NO770319L - - Google Patents

Description

Starting material for the production of 2,9-dioxatricyclo-[4.3-1.0<3>,<7>]-decanes.

The present invention relates to starting materials for the production of 2,9-dioxatricyclo-[4.3.1.0°']-decanes with the general formula:

where R^ is hydrogen and R2 is hydroxy, acyloxy or carbamoyloxy, or vice versa, or and R^ together are oxygen, as well as starting materials for the production of these compounds.

In the German published documents 19 61 433, 20 27 890, 21 29 507 and 23 06 118, 2, 9-dioxatricyclo-[4•3•1-0 •3 - 1]-decane is described which in the 8-position has a alkoxy or aralkyl group. These compounds have central depressant, hypnotic, narcotic and cardiodilatory effects.

The present invention is based on the task of providing new compounds of the above-mentioned compound group which have a new action profile.

It has surprisingly been shown that the 8-desalkoxy-, resp. 8-desaralkoxy compounds are much more centrally active than the corresponding alkyl or aralkyl derivatives. This manifests itself not only in the doses to be used, but also in the additionally strong analgesic effect that comes on par with morphine, even though the 2,9-dioxatricyclo-[4.3•1-O^'^]-decanes do not have the structure -

the characteristics of morphine or other conventional analgesics,

like for example. the methadone group, to which the reference compound propoxyphene also belongs.

Moreover, the process compounds have an anorexic effect which is superior to that of phenmetrazine (="Preludin") without being in any way related to the compound class phenylalkylamine chemically or in the other pharmacological parameters, such as e.g. toxicity and the motor stimulating activity.

The superiority of the methods is evident from the comparison of the biological activities compiled in the table between the 8-methoxy-2,9-dioxatricyclo-[4•3•1.0' ]-decanes and the corresponding 8-desalkoxy compounds as well as the corresponding, reference compounds.

The action profile of the new compounds differs from that of the known compounds in that the dampening effect is displaced in favor of a stimulating effect, and to this is added an analgesic effect component.

The procedure for producing the compounds of formula I is characterized by the fact that didrovaltatum- or didrovaltatum-containing extracts are reacted with hydrogen halide in acetic acid or in alcohol, that in the case of reaction in alcohols obtained 8-Alkoxy-, resp. 8-aralkoxy compound is transferred to the corresponding 8-hydroxy compound by cleavage of the ether bond with the help of nitric acid in acetic acid, that in both cases 8-hydroxy-3-halomethyl-4-acetoxy-10-methylene-2,9 was obtained -dioxatricyclo-[4•3•1.0 ']-decane of formula II is oxidized to the lactone of formula III, that the lactone is transferred to 1-halogen-methyl-4-methyl-7-acetoxy-2-oxa-bicyclo-[3 . 2 .1 ] -oet -3-en-g-carboxylic acid of formula IV by hydrogenolytic reduction with hydrogen and palladium/charcoal, that the acid is reduced with metal hydrides to the primary alcohol of formula V, that the alcohol by oxidative ring closure with the aid of halogen i halogenated hydrocarbons are transferred to 10-halo-10-methyl-3-halomethyl-4-acetoxy-2,9-dioxatricyclo-[4.3-l-0°' ]-decane, that the halogens are split off with hydrogen and Raney nickel in the presence of a strong base, whereby the ester is saponified at the same time, so that one obtains 3,10-dimethyl-4(3-hydroxy-2,9-dioxatricyclo-[4.3•1.0]-decane of formula VII, that one optionally transfers the compound to the acyloxy or carbarnoyloxy compound with carboxylic acid anhydride or chloride, or with alkyl isocyanates or carbamic acid esters, or optionally by oxidation of the 4-hydroxy group it transfers to the decanone of formula VIII, optionally reducing this with metal hydrides to 4a-hydroxy -decane with formula IX, that optionally with carboxylic acid anhydride or -chloride, h wh. with alkyl isocyanates or carbamic acid esters it transfers to acyloxy-, resp. the carbamoyloxy compound.

The subsequent reaction scheme illustrates the preparation of the compounds in the light of the following examples, without thereby restricting the invention to the reactants specified there.

Thus, e.g. in the preparation of the compound of formula II from didrovaltratum or Didrovaltratum-containing extracts hydrogen chloride or hydrobromic acid are used instead of hydroiodic acid.

Instead of the metal hydrides mentioned in the form when reducing acid IV to alcohol V, respectively the decanone VIII to the hydroxy compound IX, other metal hydrides can also be used, provided they leave the other functional groups in the molecule intact and also react sterically in the indicated manner.

Finally, the acid groups in the esters X and<J>XIII can also originate from other saturated and unsaturated carboxylic acids, preferably from those with 1 to 7 carbon atoms, than the indicated acetic acid; and furthermore, the nitrogen in the carbamic acid esters XI and XII can also be substituted with other alkyl, alkylene, or aralkyl groups than the methyl group, for example the nitrogen atom can also be part of a ring system.

Example 1

Preparation of 4-acetoxy-8-hydroxy-3-iodometh(yl-10-methylene-2,9-dioxatricyclo-[4.3.1.0<3>'<7>]-decane (II) from a 66% didrovaltrate - extract

425 g of extract was dissolved in acetic acid at 60°C, then a mixture of 130 ml of hydroiodic acid (57% strength) and 1 1 of water was added, and the mixture was allowed to stand for 2 hours at 6o°C with occasional stirring.

Work on it

After adding 100 g of activated carbon, suction was applied over theorite and washed thoroughly with 4 1 ether. The filtrate was added to 3 1 water, shaken well, and the ether phase was separated. This was then washed alkaline once with 2 1 water and once with soda solution (1.5 kg sodium carbonate in 8 1 water). Three water phases were then separately extracted with "3x21 ether. The combined ether phases were dried over 1 kg of sodium sulphate, treated with 100 g of activated carbon, filtered off with suction over theorit • and then evaporated in a round flask while adding 18 ml of water at 30 - 40°C in vacuum, whereupon compound II crystallized. After trituration with ether and suction over a sieve, 170 g of crude crystallisate was obtained, which is 70% of the theoretical amount.

Gross ormeal: C, 0Hn ^.0-J

12 15 5

Molecular weight: 366.14

Melting point: 152 - 156°C (Kofler, uncorrected)

[a] D +142 (methanol)

Example 2

Preparation of compound (II) from 4-acetoxy-3-iodomethyl-10-methylene-8-methoxy-2,9-dioxatricyclo-[4•3•1.0']-decane

76o g of 4-acetoxy-3-iodomethyl-10-methylene-8-methoxy-2,9^dioxatricyclo-[4.3.1.0^'^]-decane was dissolved in 2 1 of glacial acetic acid at 6o°C, and the solution was then room temperature added to a mixture of 180 ml of 64% nitric acid and 2 1 of water. The mixture was left for 2 hours at room temperature with stirring.

Processing

The reaction mixture was added to 8 1 of ether and 6 1 of water and shaken well. The ether phase was separated and washed once with 4 1 water and then with soda solution (2 kg sodium carbonate in 6 1

water). The two water phases and the soda solution were then separately extracted with 3x41 ether. The combined ether phases were dried over 2 kg of sodium sulphate and treated with 200 g of activated carbon. It was then suctioned off over theorite and thoroughly washed with ether. The filtrate was evaporated in a flask under vacuum at 30 -. 40°C while adding 36 ml of water. The resulting crystallizing residue was taken up in ether, suctioned off over a frit and thoroughly washed once with ether.

Yield: 660 g of compound II, which is 90.2% of the theoretical.

Example 3

Preparation of 4-acetoxy-3-iodomethyl-10-methylene-8-oxo-2,9-dioxatricyclo-[4.3-1.0<3>'<7>]-decane (III) from (II)

366 g of compound II was taken up in 20 l of ether at room temperature, 1250 ml of oxidation reagent was added dropwise with vigorous stirring and then stirred for a further 30 minutes.

■ Preparation of the oxidation reagent

500 g.Na2Cr207.2 H20 was taken up in 375.2 ml of 97%-ig.H2SO^

at 0°C and then, while stirring, filled with cold water to approx.

2400ml and then at room temperature exactly filled to 2500ml.

Preparation of the oxidation rate

The reaction mixture was added to 5 L of water and shaken. The ether phase was separated and washed once with 1 kg of sodium carbonate

5 1 water. The water phase and the soda solution were each extracted with

3x31 chloroform. The ether and chloroform phases were dried over sodium sulphate, treated with activated carbon and then the over-theorite was sucked off, washed with chloroform and evaporated in vacuo. The residue was taken up in ether, whereby compound III crystallized.

It was suctioned off and washed once with ether.

Yield: 310 g of compound III, which is 86% of the theoretical.

Gross formula: C,„H.,0rJ

12 lif 5

Molecular weight: 365.139

M.p.: 163 - 168°C (Kofler, uncorrected)

[a]<+p>° : +144° (methanol)

Example 4

Preparation of 1-iodomethyl-4~methyl-7-acetoxy-2-oxa-bicyclo-[3.2.1]-oct-3-ene-8-carboxylic acid (IV) from (III)

100 g of palladium/charcoal (5%) was placed in a 2 L Erlenmeyer flask, then slurried under nitrogen with 1 L of ethanol

(absolute) and immediately prehydrated with stirring at room temperature and normal pressure for 5 minutes. (Approx. 1300 ml of hydrogen was taken up.) Then 182.5 g of compound III was dissolved in 1.5 1 of absolute ethanol, and the mixture was hydrogenated for approx. 2 hours until hydrogen absorption stopped.

Hydrogen consumption: 11,200 ml.

Work on it

The catalyst was sucked off over theorite, washed with absolute ethanol, and the filtrate was evaporated in vacuum at approx. 3P°C. The residue immediately crystallized. It was triturated with ether, filtered off, washed with ether and dried. Yield: 180 g of compound IV, which is 98 >2% of the theoretical.

Gross formula: r „Hn-0rJ

12 155

Molecular weight: 366.15

Melting point: 150 - 155°C (Kofler, uncorrected)

[a]<+>^° ■: +110° (methanol)

Example 5

Preparation of 1-iodomethyl-4-methyl-7-acetoxy-8-hydroxy-meth hy1-2-oxa-bicyclo-[3.2.1]-oet-3-ene (V) from (IV)

73.2 g of compound IV was dissolved in 200 ml of tetrahydrofuran, and the solution was slowly added to 1 1 of borohydride in tetrahydrofuran (1% strength) while stirring under nitrogen at -25°C. The reaction mixture was then left at +10°C for 2 hours.

Processing

While stirring under nitrogen, first 30 ml of triethylamine was slowly added at -25°C, and then very slowly 80 ml of water was added dropwise, and then evaporated at 30 - 40°C. The residue was taken up in ether, washed with 2 x 700 ml of water and then 1 time with 90% saturated soda solution. The three aqueous phases were each subsequently extracted three times with ether. The combined ether phases were treated with sodium sulphate and activated carbon, filtered off with suction over theorite and then evaporated at 30 - 4o°C.

Yield: 1539 oily crude product (V). This was used without further purification to prepare compound VI.

Gross ormal: C^2H17'J04

Molecular weight: 352.17

Example 6

Preparation of 4~acetoxy-10-bromo-3-iodomethy1-10-methy1-2,9-dioxatricyclo-[4.3.1 ,03'7]-de c' an ( VI) from ( V)

1539(V) (crude product) was dissolved in 1100 ml of methylene chloride

in a brown round bottom flask and under vigorous stirring at -75°C slowly added a mixture of 53 ml of bromine and 110 ml of methylene chloride which had previously been cooled to -75°C.

Processing

After completion of the bromine addition, it was immediately neutralized slowly with a mixture of 168 ml of triethylamine and 110 ml of methylene chloride, washed once with water, with saturated ^2^20^- solution and potassium carbonate solution. The three aqueous phases were then individually extracted three times with methylene chloride. The combined methylene chloride phases were treated with sodium sulphate and activated carbon, filtered off with suction over theorite and evaporated in a brown round bottom flask at 30°C.

Yield: 186 g oily crude product.

Gross ormal: C^H^BrJO^

Molecular weight: 431.07

Example 7

Preparation of 4P-hydroxy-3,10-dimethyl-2,9-dioxatricyclo-[4-3-1•03'7]-decane (VII) from (VI) 86 g of water-moist Raney nickel was prehydrogenated in methanol in 1 minute at -25°C. 51.5 g of sodium hydroxide were dissolved in a little water (200 ml) and diluted with 200 ml of methanol at 0°C. This sodium chloride solution was added to the Raney nickel suspension, and then further stirred under hydrogen at -25°C. 186 g of crude product of compound VI was then dissolved in 200 ml of methanol and added to the Raney nickel suspension at 0°C. Then, with the exclusion of light at -25°C, normal pressure and stirring, hydrogen was generated for 1 to 2 hours until the hydrogen uptake was finished.

Processing

The reaction solution was filtered over theorite and washed with methanol. The filtrate was neutralized with 15 - 20 ml of acetic acid and then evaporated at approx. 50°C. The residue was taken up in ether and washed with 300 ml of water. The aqueous phase was shaken out vigorously and re-extracted 9 times with ether. The combined ether phases were treated with sodium sulfate and activated charcoal, filtered through theorite and evaporated at 50°C.

Yield: 27.22 g of oil, which is 74% of the theoretical, calculated for compound V. The oil was column chromatographed over silica gel with n-hexane with increasing addition of ether (up to 30%) as

eluent.

Gross formula: ClQH1^ 0^ Molecular weight: 184.23

r -1+20° , 00

LaJ D : +49 (in methanol)

Example 8

Preparation of 3,10-dimethy1-2,9-dioxatricyclo-[4.3.1.0 °' ]-decan-4-one (VIII) from (VII)

10 g of compound VII was dissolved in 268 ml of acetone and at

-25°C with vigorous stirring added dropwise 26.8 ral Jones reagent (oxidation reagent according to Fieser, cf. Fieser & Fieser: Reagents for Organic Synthesis, volume 1 (1967), 142), and then stirred for a further approx. 3 minutes.

Processing

After the addition of 4.02 ml of isopropanol, it was stirred for a further 5 minutes and then the reaction mixture was filtered

through theorite, and the filter material was washed thoroughly with acetone. The filtrate was neutralized with 3.5 ml of triethylamine and evaporated at 30°C. The residue was diluted with the double

amount of water and extracted with ether. The ether phase was washed

1 time with saturated potassium carbonate solution. The water phases were then

each separately after extraction IO times with ether. The combined ether phases were treated with sodium sulphate and activated carbon, filtered over theorite and evaporated in vacuo.

Yield: 3.63 g of compound VIII recrystallized from ether, which

is 36.6% of the theoretical.

Gross formula: C,_H,,0_

10 lives 3

Molecular weight: 182.21

Temp. 139 - 14o°C (Kofler, uncorrected)

[a]+p° : +54° (in methanol)

Example 9

Preparation of 4a.-hydroxy-3, 10-dimethyl-2, 9-dioxat ricyclo-

[ 4. 3- 1- O3' 7]- decane ( IX) from ( VIII)

1.5 g of lithium aluminum hydride was suspended in 90 ml of ether

and at 0°C with stirring added dropwise a solution of 7>2 g of compound VIII in 36 ml of ether. The reaction mixture was then stirred for a further 5 minutes.

Processing.

The reaction mixture was first added dropwise with 180 ml of moist ether under nitrogen and stirring, and then 6 ml of water was added and stirred for a further 10 minutes. The reaction mixture was then treated with sodium sulphate and activated carbon, filtered off with suction over theorite and evaporated in vacuo. The residue was column chromatographed over silica gel with n-hexane with increasing addition of ether (up to 50%) as eluent.

Yield: 3>25 g of oily pure product, which is 44% of the theoretical.

Gross ormeal : C,„Hn^0^

10 16 3

Molecular weight: 184.23

. [a] : +29° (in methanol)

Example 10

Preparation of 4β-acetoxy-3,10-dimethyl-2,9-dioxatricyclo-[4-3-1.03,7]-decane (V) from (VII) 10 g of crude compound VII was dissolved in a mixture of 10 ral pyridine and 10 ml of acetic anhydride and left overnight at room temperature.

Processing

The reaction mixture was slowly added at 0°C while stirring with 10 ml of ethanol, stirred for a further 30 minutes at room temperature, evaporated at 80°C and after renewed absorption with 20 ml of ethanol again evaporated at 80°C. The residue was column chromatographed on silica gel with n-hexane with increasing addition of ether (up to 20%) as eluent.

Yield: 4.0 g of oily pure product.

Gross formula: C „Hnn0,

12 18 4

Molecular weight: 226.26

[a]<+>^°: +56° (in methanol)

Example 11

First in Iling of 4(3-meth hy lea rbamoyloxy-3 ,10-dimethy 1 -2 , 9-dioxa - tricyclo-[ 4. 3. 1- 03, 7]- decane (XI) from (VII) 5 g of compound VII was dissolved in 50 ml of methylene chloride, 6.8 ml of methyl isocyanate and 1.089 phenylmercuric acetate were added and then left at room temperature for 1 - 2 hours.

Processing

After adding 10 ml of ethanol, the reaction mixture was evaporated. The residue was purified by column chromatography on silica gel with carbon tetrachloride under increasing addition of chloroform (up to 50%).

Yield: 2.89 g of pure product recrystallized from ether, which is 44.1% of the theoretical.

Gross ormel: C, „Hn ^0, N

12 19 4

Molecular weight: 241.27

M.p.: 104°C (Kofler, uncorrected)

o

[al+D +75° (in methanol)

Example 12

Preparation of 4ci--methylcarbamoyloxy-3,10-dimethyl-2,9-dioxa-tricyclo-[4.3.1.0<3>,<7>]-decane (XII) from (IX) 5 g of compound IX was dissolved in 50 ml methylene chloride, added 4.65 ml methyl isocyanate and 1.089 phenylmercuric acetate and left at room temperature for approx. 2 hours.

Processing

The reaction mixture was added with 10 ml of ethanol and evaporated.

The residue was purified by column chromatography on silica gel eluting with 20 - 50% chloroform in carbon tetrachloride.

Yield: 3.0 g of crystalline compound of formula XII, which

is 45.7% of the theoretical.

Gross formula: C,„H,nO,N

• 12 19 4

Molecular weight: 241.27

Temp. 109°C (Kofler, uncorrected)

[a]<+20>°: +26° (in methanol)

Example 13

Preparation of 4a-acetoxy-3,10-dimethyl1-2,9-dioxatricyclo-[4.3.1.03, 7]- decane ( XIII) from ( IX)

8.0 g of compound IX was added to a mixture of 8 ml of pyridine and 8 ml of acetic anhydride and left overnight at room temperature.

Work on it

The reaction mixture was diluted with 3 times its volume of chloroform. This solution was first shaken with dilute hydrochloric acid in ice, and then with half-saturated potassium carbonate solution. The aqueous solutions were subsequently extracted separately with chloroform. The combined chloroform phases were dried with sodium sulfate and treated with activated carbon, then filtered and the filtrate evaporated in vacuo. The residue was column chromatographed over silica gel with n-hexane with increasing addition of ether (up to 30%). Compound XIII could be crystallized from ether. Yield: 7.16 g of crystallisate, i.e. 73.1% yield.

Gross flour : ' C, „H.. _0,

. 12 18 4

Molecular weight: 226.26

M.p.: 85°C

[a]*"^ : +49° in methanol Example 14; Preparation of 4(3-isopropylcarbamoyloxy^3 ,10-dimethyl-2 9-dioxatricyclo-[ 4. 3. 1. 0 ''}- decane ( XIV) from (VII); 1 g of compound VII was dissolved in 9 ml of dichloromethane, 1.8 ml of isopropyl isocyanate and 180 mg of phenylmercuric acetate were added as a catalyst, and the reaction mixture was then refluxed for 2 hours. After adding 5 ml of methanol, the mixture was evaporated. The residue was column chromatographed over silica gel with n-hexane with increasing addition of ether (up to 100%). After evaporation of the eluate, 1.1 g of oily isopropyl carbamate was obtained, which is 7552% of the theoretical amount. ; Crude formula : C, , H_„NO,;14 23 4 ;Molecular weight: 269.44;[a]^2 : +65.5° in methanol;Example 15 ;Preparation of 4(3-f enylca rbamoyloxy-3 , 10-dimethyl-2,9-dioxa-tricyclo-[4.3.1.0<3>'<7>]-decane (XV) from (VII); 1 g of compound VII was dissolved in 9 ml of dichloromethane, added 1.8 ml of phenyl isocyanate and 180 mg of phenylmercuric acetate as catalyst, and the reaction mixture was then stirred at room temperature for 2 hours. After adding 5 ml of methanol, the mixture was evaporated. The residue was column chromatographed over silica gel with n-hexane with increasing addition of ether (up to 100%). After evaporation of the eluate, 1.5 g of crystalline phenylcarbamate was obtained from ether, which is 91% of the theoretical. Crude formula: C-^H^NO^; Molecular weight: 303.35; M.p.: 240°C; [a]22 : -72.7° in methanol.; Example 16; Preparation of 4(3-r>- butylcarbamoyloxy-3,10-dimethyl-2,9-dioxa-tricyclo-[4.3.1.03,7]-decane (XVI) from (VII); 1 g of compound VII was dissolved in 9 ml of dichloromethane, added 1.8 ml of n-butyl isocyanate and 180 mg of phenylmercuric acetate as catalyst, and the reaction mixture was then stirred for 2 hours at room temperature. After the addition of 5 ml of methanol, the mixture was evaporated. The residue was column chromatographed over silica gel with n-hexane under increasing addition of ether (up to 100%). After evaporation of the eluate, 0.99 g of oily n-butyl carbamate was obtained, which is 58.44% of the theoretical amount. ; Crude formula: C^H^NO^; Molecular weight: 283.36 ; 22 o ; [a] D : +64.0 in methanol; Example 17; Preparation of 4P-propionyloxy-3,10-dimethyl1-2,9- dioxatricyclo - ;[ 4. 3. 1- 03, 7]- decane ( XVII) from ( VII); 9 g of compound VII was dissolved in a mixture of 9 ml. pyridine and 9 ml of propionic anhydride and left at room temperature for 4 hours. After dilution with chloroform, the reaction mixture was added to ice water and acidified with dilute hydrochloric acid, and then shaken. After separation of the water phase, the chloroform phase was washed 1 time with water and 1 time with diluted soda solution. The water phases were each separately extracted 3 times with chloroform. After evaporation of the chloroform phase, the residue was column-chromatographed over silica gel with n-hexane with increasing addition of up to 50% ether. After evaporation of the eluate, 4.2 g of oily compound (XVII) was obtained, which is 36% of the theoretical amount. _ ; ; Gross formula: C. 0H__r>,;13 20 4 ;Molecular weight: 240.30;[a]<2>3:+67° in chloroform;Example 18;Preparation of 4a-isopropylearbamoyloxy-3,10-dimethyl1-2,9 -dioxatricyclo-[ 4. 3. 1, 03' 7]- decane ( XVIII) from ( IX) 1 g of compound IX was dissolved in 10 ml of dichloromethane, 2 ml of isopropyl isocyanate and 220 mg of phenylmercuric acetate were added as a catalyst, and the reaction mixture was then set aside at room temperature for 10 hours. After adding 5 ml of methanol, the mixture was evaporated. The residue was column chromatographed over silica gel with n-hexane with increasing addition of ether. After evaporation of the eluate, 1.22 g of oily isopropyl carbamate was obtained, which is 83.5% of the theoretical amount. ; Gross ormel : C-^H N0^_;Molecular weight:. 269.44; [a]<22>+30° in methanol; Example 19; Preparation of 4a.-phenylcarbamoyloxy-3,10-dimethyl 1-2,9-dioxa-tricyclo-[4. 3. 1. 03 ' 7] - decane (XIX) from (IX); 1 g of compound IX was dissolved in 10 ml of dichloromethane, 2 ml of phenylisocyanate and 220 mg of phenylmercuric acetate were added as catalyst, and the reaction mixture was then allowed to stand at room temperature for 10 hours. After adding 5 ml of methanol, the mixture was evaporated. The residue was column chromatographed over silica gel with carbon tetrachloride with increasing addition of chloroform. After evaporation of the eluate, 0.719 of oily phenylcarbamate was obtained, which is 43.3% of the theoretical amount. ; Crude formula: C^^H^NO^ ;Molecular weight: 303.35;[a]<22>+28° in methanol;Example 20;Preparation of 4a-n-butylcarbamoyloxy-3,10-dimethyl-2,9- dioxa-. tricyclo-[4. 3 .1.03 '7]-decane (XX) from (IX); 1 g of compound IX was dissolved in 10 ml of dichloromethane, 2 ml of n-butyl isocyanate and 220 mg of phenylmercuric acetate were added as a catalyst, and the reaction mixture was then allowed to stand at room temperature in 10 hours. After adding 5 ml of methanol, the mixture was evaporated. The residue was column chromatographed over silica gel with n-hexane while increasing the addition of ether. After evaporation of the eluate, 0.979 g of oily butyl carbamate was obtained, which is 63% of the theoretical amount. ; Crude formula: H^NO^; Molecular weight: 283.36; [a]<22>: +45° in methanol; Example 21; Preparation of 4a-propionyloxy-3,10-dimethyl1-2,9-dioxatricyclo-[ 4 3. 1. 03, 7]-decane (XXI) from (IX); 13.36 g of compound IX was dissolved in a mixture of 13.36 ml of pyridine and 13.36 ml of propionic anhydride and left overnight at room temperature. After dilution with chloroform, the reaction mixture was added to ice water and acidified with dilute hydrochloric acid, and then shaken. After separation of the water phase, the chloroform phase was washed once with water and once with diluted soda solution. The aqueous phases were each subsequently extracted 3 times with chloroform. After evaporation of the chloroform phases, the residue was column-chromatographed on silica gel with n-hexane while increasing the addition of up to 50% ether. After evaporation. 11.35 g of oily compound XXI was obtained from the eluate, which is 64.5% of the theoretical amount. ; ; Gross formula: C,oHo„0, ;13 20 4 ;Molecular weight: 240.30 ;20 ;• [a]D : +30° in chloroform *

Claims (4)

1. Starting material for the production of 2, 9-dioxat r lcyclo-[4. 3.1.0J' /j-^lcaffeTf39- K: a rect erized in that they have the formula: where Hal is halogen, and Ac is acyl. 2. Starting material according to claim 1, characterized in that it is 4-acetoxy-8-hydroxy-3-iodomethyl-10-methylene-2,9-dioxatricyclo-[4•3•1'0 q ' 7]— decane. 3. Process for the production of 4-acetoxy-8-hydroxy-3-iodomethylene-10-methylene-2,9-dioxatricyclo-[4•3•1.0 q' 7]-decane according to claim 1 or 2, characterized in that didrovaltratum or didrovaltratum-containing extracts are reacted with hydrohalic acid in glacial acetic acid. 4. Process for the production of 4-acetoxy-8-hydroxy-3-iodomethyl-10-methylene-2,9-dioxatricyclo-[4.3.1.03'7]-decane according to claim 1 or 2, characterized in that 4- acetoxy-3-iodomethyl-10-methylene-8-methoxy-2,9-dioxa ricyclo-[4•3•1•0 q 7]-decane is reacted with nitric acid in glacial acetic acid..