JPS5998043A - Optical resolution of (+-)-p-methoxy-alpha-methylbenzylamine - Google Patents
Optical resolution of (+-)-p-methoxy-alpha-methylbenzylamineInfo
- Publication number
- JPS5998043A JPS5998043A JP20600382A JP20600382A JPS5998043A JP S5998043 A JPS5998043 A JP S5998043A JP 20600382 A JP20600382 A JP 20600382A JP 20600382 A JP20600382 A JP 20600382A JP S5998043 A JPS5998043 A JP S5998043A
- Authority
- JP
- Japan
- Prior art keywords
- methoxy
- methylbenzylamine
- acetate
- alpha
- optical resolution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 230000003287 optical effect Effects 0.000 title claims abstract description 27
- JTDGKQNNPKXKII-UHFFFAOYSA-N 1-(4-methoxyphenyl)ethanamine Chemical compound COC1=CC=C(C(C)N)C=C1 JTDGKQNNPKXKII-UHFFFAOYSA-N 0.000 title description 15
- 239000013078 crystal Substances 0.000 claims abstract description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims abstract description 18
- DDYXFMVOQBWKIR-UHFFFAOYSA-N acetic acid;1-(4-methoxyphenyl)ethanamine Chemical compound CC(O)=O.COC1=CC=C(C(C)N)C=C1 DDYXFMVOQBWKIR-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims description 11
- FAFRRWWYYOPZBO-UHFFFAOYSA-N acetic acid;n-methyl-1-phenylmethanamine Chemical compound CC(O)=O.CNCC1=CC=CC=C1 FAFRRWWYYOPZBO-UHFFFAOYSA-N 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 abstract description 15
- 239000003085 diluting agent Substances 0.000 abstract description 7
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 239000007788 liquid Substances 0.000 abstract description 5
- 238000002425 crystallisation Methods 0.000 abstract description 4
- 230000008025 crystallization Effects 0.000 abstract description 3
- 239000000203 mixture Substances 0.000 abstract description 2
- 239000003960 organic solvent Substances 0.000 abstract description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 2
- 238000010899 nucleation Methods 0.000 abstract 2
- 230000000694 effects Effects 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 150000003839 salts Chemical class 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- 159000000021 acetate salts Chemical class 0.000 description 2
- WHMLOJLHHRDQIL-UHFFFAOYSA-N acetic acid;1-phenylethanamine Chemical compound CC(O)=O.CC(N)C1=CC=CC=C1 WHMLOJLHHRDQIL-UHFFFAOYSA-N 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 2
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 description 1
- RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 description 1
- 238000012824 chemical production Methods 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000011549 crystallization solution Substances 0.000 description 1
- 229960001270 d- tartaric acid Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- -1 methoxy-α-methylbenzylamine acetate Chemical compound 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- KRKUIQZXRHNRRY-UHFFFAOYSA-N n-methoxy-1-phenylethanamine Chemical compound CONC(C)C1=CC=CC=C1 KRKUIQZXRHNRRY-UHFFFAOYSA-N 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
ある種の医薬、農薬あるいは食品添加剤のなかには光学
活性な化合物が少なくない。そしてこのような化合物を
化学的に製造する場曾には、光学分割という手続きか必
要とされる場合が多い。従来、このような化付物の光学
分割には、キニーネやブルシンのような天然光学分割剤
が多く用いられて来たが、近年、α−メチルベンジルア
ミンや１−フェニル−２−（ｐ−１リル）エチルアミン
などの合成光学９分割剤の重要性もとみに高まってきた
。DETAILED DESCRIPTION OF THE INVENTION Among certain pharmaceuticals, agricultural chemicals, and food additives, there are many optically active compounds. In the chemical production of such compounds, a procedure called optical resolution is often required. Conventionally, natural optical resolving agents such as quinine and brucine have often been used for the optical resolution of such compounds, but in recent years, α-methylbenzylamine and 1-phenyl-2-(p- The importance of synthetic optical 9-resolving agents such as ethylamine has been increasing.
本発明は、このような合成光学分割剤の１つとして新た
な用途が開けるものと期待できる化合物であるｐ−メト
キシ−α−メチルベンジルアミンの光学活性体を経済的
に製造する方法に関するものであり、さらに詳しくは、
（−１−ｐ−メトキシ−α−メチルベンジルアミンの簡
便な光学分割法に関するものである。The present invention relates to a method for economically producing an optically active form of p-methoxy-α-methylbenzylamine, which is a compound that is expected to have new uses as one of such synthetic optical resolution agents. Yes, for more details,
(Relates to a simple optical resolution method for -1-p-methoxy-α-methylbenzylamine.
既に知られている（＋）−ｐ−メトキシ−α−メチルベ
ンジルアミンの光学分割法としては、たとえば、ｄ−酒
石酸を分割剤として用いる方法（Ｒ，Ｄ、Ｇｕｔｈｒｉ
ｅ ａｎｄ ＩＬ Ｌ、 Ｈｅｄｒｉｃｋ 。Already known optical resolution methods for (+)-p-methoxy-α-methylbenzylamine include, for example, a method using d-tartaric acid as a resolving agent (R, D, Guthri et al.
e and IL L, Hedrick.
Ｊ、 Ａｍ、、Ｃｈｅｍ、 Ｓｏｃ、 、 ９５．２９
７１＜ １９７３ ）’ ）等がメジ、この方法によれ
ば、一方の対掌体を純粋に得るためには数回の再結晶操
作を必要とし、他方の対掌体を純粋に得るためには溶媒
を変えてさらに数回の再結品を必要とするなど煩雑な操
作を伴なう欠点かある。J, Am, , Chem, Soc, , 95.29
According to this method, several recrystallization operations are required to obtain one enantiomer pure, and to obtain the other enantiomer pure. It has the disadvantage of requiring complicated operations such as changing the solvent and reconsolidating several times.
本発明者らは、（１’ ｐ−メトキシ−α−メチルベン
ノルアミンの光学分割法について種種検削をヰねた結果
、（”）’ｐ−メトキシーα−メチルベンノルアミンを
その酢酸塩とすることにより、接種法による優先晶出法
の適用が可能になり、（至）−ｐ−メトキシ−α−メチ
ルベンジルアミンを高純度、高収率で容易に光学分割で
きることを見い出し、本発明を完成した。The present inventors conducted various tests on the optical resolution method of (1'p-methoxy-α-methylbenolamine) and found that ('')'p-methoxyα-methylbenolamine was used as its acetate salt. By this, it became possible to apply the preferential crystallization method using the inoculation method, and it was discovered that (to)-p-methoxy-α-methylbenzylamine could be easily optically resolved with high purity and high yield, and the present invention was completed. did.
すなわち本発明は、（ｆ） ’ｐ−メトキシーα−メ
チルベンジルアミン・酢酸塩の過飽オ目溶液に（＋）−
または（−）−ｐ−メトキシ−α−メチルベンジルアミ
ン・酢酸塩の結晶を接種することによって（＋）−また
は（→−ｐ−ノドキシーα−メチルベンジルアミン・酢
酸塩を優先的に晶出させ、得られた塩を常法に従いアル
カリで分解することを特徴とする（ｆ）−ｐ−メトキシ
−α−メチルベンジルアミンの光学分割法である。That is, the present invention provides (f) a supersaturated solution of p-methoxy α-methylbenzylamine acetate with (+)-
Or, by inoculating crystals of (-)-p-methoxy-α-methylbenzylamine acetate, (+)- or (→-p-nodoxy-α-methylbenzylamine acetate is preferentially crystallized. is an optical resolution method for (f)-p-methoxy-α-methylbenzylamine, which is characterized by decomposing the obtained salt with an alkali according to a conventional method.
本発明の実施にあれっては、（＝Ｌ）ｐ−メトキシ−α
−メチルベンノルアミンまたは、一方の光学活性体を過
剰に含有する（支）−ｐ−メトキシ−α−メチルベンジ
ルアミンと酢酸との塩を液体希釈剤に加熱溶解して過飽
和とする。これに光学活性なｐ−メトキシ−α−メチル
ベンノルアミンと酢酸との塩の結晶を少量接種し、接種
した光学活性体と同種の光学活性体の塩を晶出させ分離
する。この場合、ｐ−メトキシ−α−メチルベンジルア
ミンの酢酸塩は別途に調製したものを液体希釈剤に溶解
してもよいし、あるいは直接ｐ−メトキシ−α−メチル
ベンジルアミンと酢酸とを液体希釈剤に加えて該液体希
釈剤中で塩を生成させ溶解させてもよい。In carrying out the present invention, (=L)p-methoxy-α
-Methylbennolamine or a salt of (sub)-p-methoxy-α-methylbenzylamine containing an excess of one of the optically active substances and acetic acid is heated and dissolved in a liquid diluent to make it supersaturated. A small amount of crystals of a salt of optically active p-methoxy-α-methylbenolamine and acetic acid is inoculated into this, and a salt of an optically active substance of the same type as the inoculated optically active substance is crystallized and separated. In this case, the acetate of p-methoxy-α-methylbenzylamine may be prepared separately and dissolved in a liquid diluent, or directly diluted with p-methoxy-α-methylbenzylamine and acetic acid. In addition to the agent, a salt may be formed and dissolved in the liquid diluent.
光学分割すべきｐ−メトキシ−α−メチルベンジルアミ
ンが一方の光学活性体を過剰に含有する場合には、これ
と同種の九学活性体塩全接種するのが好ましく、また過
剰の度合が大きい場合には活性体塩の接種を行わず自然
品出によっても活性体の塩を得ることができる。When the p-methoxy-α-methylbenzylamine to be optically resolved contains an excess of one of the optically active forms, it is preferable to inoculate all the salts of the nine active substances of the same type, and the degree of excess is large. In some cases, the active salt can also be obtained by natural production without inoculation with the active salt.
次に１愛先晶出後の母液に（＋Ｊ−ｐ−メトキシーα−
メチルベンジルアミン・酢酸塩を補光して、前回接線し
た光学活性体と反対の旋光性を持つｐ−メトキシ−α−
メチルベンジルアミン・酢版塩の結晶を接種して、これ
と同種の光学活性体の塩の結晶を晶出させこれを分離す
る。以下、同様の操作を繰シ返すことにより、ラセミま
たは低光学純度のｐ−メトキシ−α−メチルベンジルア
ミンを酢酸塩として答易かり完全に光学分割することが
できる。Next, add (+J-p-methoxy α-
By supplementing methylbenzylamine acetate, p-methoxy-α- which has optical rotation opposite to that of the previously tangential optically active substance is obtained.
Crystals of methylbenzylamine acetate salt are inoculated, and crystals of the same type of optically active salt are crystallized and separated. Thereafter, by repeating the same operation, racemic or low optical purity p-methoxy-α-methylbenzylamine can be easily and completely optically resolved as an acetate salt.
前記の液体希釈剤としては、通常、メタノール、エタノ
ール、１−プロパツール、２−ノロパノール、アセトン
およびこれらの有機希釈剤と水との混合溶媒などが使用
されるが、好ましくは２−プロパツールを用いると効率
よく光学分割が行われる。As the liquid diluent, methanol, ethanol, 1-propanol, 2-propanol, acetone, a mixed solvent of these organic diluents and water, etc. are usually used, but 2-propanol is preferably used. When used, optical separation can be performed efficiently.
更に、ｐ−メトキシ−α−メチルベンジルアミンの酢酸
塩の溶液に冷時においても十分な溶解性をもつ遊離の（
＝Ｂ−ｐ−メトキシーα−メチルベンジルアミンを共存
させる事によシ、効率よく、安定して光学活性な堰を晶
出させる事ができる。これは、共存させた（±−ｐ−メ
トキシーα−メチルベンジルアミンが酢酸塩と平衡状態
にあシ、対掌体の晶出圧力に対して緩衝的に作用するの
で、晶出液と接種した活性体の塩の結晶相とは終始安定
した相平衡関係を保持するためである。Furthermore, free (
By coexisting =Bp-methoxyα-methylbenzylamine, an optically active weir can be efficiently and stably crystallized. This is because ±-p-methoxy α-methylbenzylamine is in equilibrium with acetate and acts as a buffer against the crystallization pressure of the enantiomer, so it was inoculated with the crystallization solution. This is to maintain a stable phase equilibrium relationship with the crystal phase of the active salt from beginning to end.
また、光学活性な塩を晶出させる際に、母液を攪拌する
ことにより、晶出時間を大幅に短縮することも可能であ
る。Further, when crystallizing the optically active salt, it is also possible to significantly shorten the crystallization time by stirring the mother liquor.
このようにして得られた光学活性ｐ−メトキシーα−メ
チルベンジルアミンの酢酸塩は、必要あればこれを再結
晶し、水酸化ナトリウムまたは水酸化カリウム等のアル
カリ水溶液を作用させて分解し、遊離した光学活性ｐ−
メトキシ−α−メチルベンジルアミンを二一チル、ベン
ゼン等の有機溶媒で抽出して蒸留すると、光学的に純粋
な（＋）−および１−）−ｐ−メトキシ−α−メチルベ
ンジルアミンを得ることができる。The optically active p-methoxy α-methylbenzylamine acetate thus obtained is recrystallized if necessary and decomposed by the action of an alkaline aqueous solution such as sodium hydroxide or potassium hydroxide to release the optically active p-methoxy α-methylbenzylamine acetate. The optically active p-
Optically pure (+)- and 1-)-p-methoxy-α-methylbenzylamine can be obtained by extracting methoxy-α-methylbenzylamine with an organic solvent such as 21-methyl and benzene and distilling it. I can do it.
以下、実施例を挙げ本発明方法を更に詳細に説明するが
、本発明はこれによシ限定されるものではない。Hereinafter, the method of the present invention will be explained in more detail with reference to Examples, but the present invention is not limited thereto.
実施例１
（−Ｌ）−ｐ−メトキシ−α−メチルベンジルアミン・
酢酸塩１２．９３．９および（±−ｐ−メトキシーα−
メチルベンジルアミン１８．５１ｇに２−）ロバノール
４５蔵を加え、加熱溶解後、約５分曲放冷した。該溶液
に、別途に調製した純粋な（＋）−ｐ−メトキシ−α−
メチルベンジルアミン・酢酸塩の結晶（ｍｐ、’１２７
〜１３０°Ｏ，［α］”＋２１．２°（Ｃ１０、３５
ＭｅＯＨ） ） １５．２７ｔＴ９ ｋ接種し、母液を
１２０回／分の速度で１時間攪拌し、析出した結晶をＥ
取して（＋１−ｐ−メトキシ−α−メチルベンノルアミ
ン１．３６９を得た。〔α〕２３°２＋１７．８゜３５
（ｃ 、、、１．０、ＭｅＯＨ）光学純度８４．０％前
記の結晶をＦ別した母液に（ｌｘ）−、ｐ−メトキシ−
α−メチルベンジルアミン・酢酸塩１、３６ ｇを追加
し、加熱溶解して約５分間放冷後、別途に調製した純粋
な（−）−ｐ−メトキシ−α−メチルベンジルアミン・
酢酸塩の結晶（ｍｐ、 １２８〜１３０°Ｃ，［α：］
２２−２１．２゜３５
（ｃ １．０ 、ＭｅＯＨ） ） １９．４〜９を
接種し、同様に１時間攪拌した。析出した結晶を戸数し
て（−）−ｐ−メトキシ−α−メチルベンジルアミン・
酢酸塩２．４２．！７を得た。〔α〕１６３−５５−１
７．７° （ｃ １．０ 、ＭｅＯＨ）光学純度８３
５係
以下、同様な操作を繰り返し、光学純度８０〜９０壬の
（＋）−および（−）−ｐ−メトキシ−α−メチルベン
ジルアミン・酢酸塩を３〜４ｇずつ交互に得た。Example 1 (-L)-p-methoxy-α-methylbenzylamine.
Acetate 12.93.9 and (±-p-methoxy α-
45 grams of 2-) lovanol was added to 18.51 g of methylbenzylamine, dissolved by heating, and then left to cool for about 5 minutes. To this solution, separately prepared pure (+)-p-methoxy-α-
Crystals of methylbenzylamine acetate (mp, '127
~130°O, [α]”+21.2° (C10, 35 MeOH)
(+1-p-methoxy-α-methylbenolamine 1.369 was obtained. (lx)-, p-methoxy-
Add 1.36 g of α-methylbenzylamine acetate, dissolve with heat and let cool for about 5 minutes, then add pure (-)-p-methoxy-α-methylbenzylamine prepared separately.
Acetate crystals (mp, 128-130°C, [α:]
22-21.2°35 (c 1.0, MeOH)) 19.4-9 was inoculated and stirred in the same manner for 1 hour. The precipitated crystals were separated into (-)-p-methoxy-α-methylbenzylamine.
Acetate 2.42. ! I got a 7. [α]163-55-1
7.7° (c 1.0, MeOH) Optical purity 83
The same operation was repeated for Section 5 and below to alternately obtain 3 to 4 g each of (+)- and (-)-p-methoxy-α-methylbenzylamine acetate having an optical purity of 80 to 90 mm.
実施例２
光学純度８６，８係の（−）−ｐ−メトキシ−α−，Ｉ
ｆルベンジルアミン・酢酸塩４．８４９を２−プロパツ
ール１０．０ｍＡに加熱溶解し、（−）−ｐ−メトキシ
−α−メチルベンジルアミン・酢酸塩の結晶３〜９を接
種し、−夜装置した後析出した結晶をＰ取して、ＯＰ−
メトキシ−α−メチルベンジルアミン・酢酸塩３．９０
Ｉを得た。〔α］１８−１９．７° （ｃ １．０
、ＭｅＯＨ）３５
光学純度９２９係 用いたｐ−メトキシ−α−メチルベ
ンジルアミン中に含まれる（−）一体に対する収率は８
６．３循。Example 2 (-)-p-methoxy-α-,I with optical purity of 86.8
f-rubenzylamine acetate 4.849 was heated and dissolved in 2-propanol 10.0 mA, inoculated with crystals 3 to 9 of (-)-p-methoxy-α-methylbenzylamine acetate, and overnight. After using the device, the precipitated crystals were collected and OP-
Methoxy-α-methylbenzylamine acetate 3.90
I got I. [α] 18-19.7° (c 1.0
, MeOH) 35 Optical purity: 929 The yield based on the (-) monomer contained in the p-methoxy-α-methylbenzylamine used was 8
6.3rd cycle.
こうして借ら′ｆした（−）−ｐ−メトキシ−α−メチ
ルベンジルアミン・酢酸塩のうち、１６０ｇを１規定水
酸化ナトリウム水溶液９．４ｍｌに溶解し、遊離した（
−）−ｐ−メトキシ−α−メチルベンジルアミンをベン
ゼンで抽出し、水酸化ナトリウムで乾燥させた後、ベン
ゼンを減圧留去し、蒸留によって（−）−ｐ−メトキシ
−α−メチルベンジルアミン１．１７ ｇを得り。Of the thus borrowed (-)-p-methoxy-α-methylbenzylamine acetate, 160 g was dissolved in 9.4 ml of 1N aqueous sodium hydroxide solution to liberate (
-)-p-Methoxy-α-methylbenzylamine is extracted with benzene, dried over sodium hydroxide, the benzene is distilled off under reduced pressure, and (-)-p-methoxy-α-methylbenzylamine 1 is extracted with benzene. Obtained .17 g.
ｂｐ、 １２５°Ｏ（３６ｍｍＨｇ ）α賃−３２，９
゜（１，ｄｍ 、 ｎＱａｔ ）、光学純度９３．７％
、塩からの回収垂は９８．０係であった。bp, 125°O (36mmHg) α -32,9
°(1,dm, nQat), optical purity 93.7%
The amount recovered from salt was 98.0.
実施例３
光学純度８６，８壬の（＋）−ｐ−メトキシ−α−メチ
ルベンジルアミン・酢酸塩４．６４ 、ｆを２−プロパ
ツール１０．０−に加熱溶解し、（＋）−ｐ−メトキシ
−α−メチルベンジルアミン・酢酸塩の結晶３１１９を
接種し、３時間放置した後、析出した結晶を戸数して、
（＋）−ｐ−メトキシ−α−メチルベンジルアミン・酢
酸塩３５４ｇを得た。〔α］”＋２１．０°（Ｃ１０、
３５
ＭｅＯＨ） 、光学純度９９．１＝１ 用いたｐ−メ
トキシ−α−メチルベンジルアミン中に含まれる（刊一
体に対する収率は８１．６係こうして得られた（＋）−
ｐ−メトキシ−α〜メチルベンジルアミン・酢酸塩のう
ち、１６６ｇを１規定水酸化ナトリウム水溶液９．４ｍ
ｌに溶かし、遊離した（＋）−ｐ−メトキシ−α−メチ
ルベンジルアミンをベンゼンで抽出し、水酸化ナトリウ
ムで乾燥させた後、ベンゼンを減圧留去し、蒸留によっ
て（＋）−ｐ−メトキシ−α−メチルベンジルアミン１
．１７ｇを得た。Example 3 (+)-p-methoxy-α-methylbenzylamine acetate 4.64, f with an optical purity of 86.8 was heated and dissolved in 2-propanol 10.0- -Methoxy-α-methylbenzylamine acetate crystal 3119 was inoculated and left to stand for 3 hours, and the precipitated crystals were counted.
354 g of (+)-p-methoxy-α-methylbenzylamine acetate was obtained. [α]”+21.0° (C10,
(+)-
166g of p-methoxy-α~methylbenzylamine acetate was added to 9.4ml of 1N aqueous sodium hydroxide solution.
The liberated (+)-p-methoxy-α-methylbenzylamine was extracted with benzene, dried over sodium hydroxide, the benzene was distilled off under reduced pressure, and (+)-p-methoxy -α-methylbenzylamine 1
．． 17g was obtained.
ｂｐ、 ］、 ２８°Ｃ（４，２ｍｍＨｇ ）αｇ−３
４，８°（１ｄｒｒ＋Ｘｎｅａｔ ）、光学純度９９１
壬 塩からの回収率は９８．２係であった。bp, ], 28°C (4,2 mmHg) αg-3
4.8° (1drr+Xneat), optical purity 991
The recovery rate from the salt was 98.2.
実施例４
（＋Ｊ−ｐ−メトキシーα−メチルベンジルアミン・酢
酸塩１．５１．９および、（ｆ）−ｐ−メトキシ−α−
メチルベンジルアミン１．０８．？’＆９９係エタノー
ル３０−に加熱溶解し、約５分間放冷後、（＋）−ｐ−
メトキシ−α−メチルベンジルアミン・酢酸塩の結晶２
．８ ｍ９を接種し、４５分間静置後、析出した結晶を
洲取して（＋）−ｐ−メトキシ−α−メチルベンジルア
ミン・酢酸塩１１．８ ｍ９を得た。〔α］２８＋ １
４．４゜３５
（ｃ Ｏ，２、ＭｅＯＨ）光学純度６７．９１前記の結
晶をＰ別した母液に田−ｐ−メトキシ−α−メチルベン
ジルアミン・酢酸塩を！ ２．２ ｍｇ追加し、加熱溶
解して約５分間放冷した。（−）−ｐ−メトキシ−α−
メチルベンジルアミン・酢酸塩の結晶３，５ノψを接種
し、３時間静直後、析出した結晶を渥取して、（−１ｐ
−メトキシ−α−メチルベンジルアミンｅ酢酸塩７０．
５ ｍ９を得た。〔α〕２７ ｓ、 ９° （Ｃ３５
１、４、ＭｅＯＨ）光学純度４２．０％以下、同様な操
作を繰シ返し、光学純度８０〜９０係の（＋）−および
０−ｐ−メトキシ−α−メチルベンジルアミン・酢酸塩
を５０〜１５０ ｍ９ずつ交互に得た。Example 4 (+J-p-methoxy α-methylbenzylamine acetate 1.51.9 and (f)-p-methoxy-α-
Methylbenzylamine 1.08. ? '& 99 ethanol 30- by heating, after cooling for about 5 minutes, (+)-p-
Crystals of methoxy-α-methylbenzylamine acetate 2
．． After inoculating 8 m9 of the mixture and allowing it to stand for 45 minutes, the precipitated crystals were collected to obtain 11.8 m9 of (+)-p-methoxy-α-methylbenzylamine acetate. [α]28+1
4.4゜35 (c O, 2, MeOH) Optical purity 67.91 P-separated mother liquor from the above crystals was mixed with p-methoxy-α-methylbenzylamine acetate! 2.2 mg was added, dissolved by heating, and allowed to cool for about 5 minutes. (-)-p-methoxy-α-
3.5 ψ of methylbenzylamine acetate crystals were inoculated, and immediately after 3 hours, the precipitated crystals were collected and (-1p
-Methoxy-α-methylbenzylamine e acetate 70.
5 m9 was obtained. [α] 27 s, 9° (C35 1,4, MeOH) Optical purity 42.0% or less. Repeat the same operation to obtain (+)- and 0-p-methoxy- with optical purity 80-90. 50 to 150 m9 of α-methylbenzylamine acetate were alternately obtained.
特許出願人 野 平 博 之Patent applicant Hiroshi Nono
Claims (1)
塩の過飽和溶液に（＋）−または（−）−ｐ−メトキシ
−α−メチルベンジルアミン・酢酸塩の結晶を接種する
ことによって、（＋）−または（→−ｐ−メトキシーα
−メチルベンジルアミン・酢酸塩を優先的に晶出させる
ことを特徴とする（ｆ）−ｐ−メトキシ−α−メチルベ
ンジルアミンの光学分割法。By inoculating a supersaturated solution of (+)- or (-)-p-methoxy-α-methylbenzylamine acetate with crystals of (]-]p-methoxy-α-methylbenzylamine acetate, (+ )- or (→-p-methoxy α
(f) An optical resolution method for -p-methoxy-α-methylbenzylamine, characterized by preferentially crystallizing methylbenzylamine acetate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20600382A JPS5998043A (en) | 1982-11-26 | 1982-11-26 | Optical resolution of (+-)-p-methoxy-alpha-methylbenzylamine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20600382A JPS5998043A (en) | 1982-11-26 | 1982-11-26 | Optical resolution of (+-)-p-methoxy-alpha-methylbenzylamine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS5998043A true JPS5998043A (en) | 1984-06-06 |
Family
ID=16516292
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP20600382A Pending JPS5998043A (en) | 1982-11-26 | 1982-11-26 | Optical resolution of (+-)-p-methoxy-alpha-methylbenzylamine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5998043A (en) |
-
1982
- 1982-11-26 JP JP20600382A patent/JPS5998043A/en active Pending
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