Method for producing (R)-1,1,3-trimethyl-4-aminoindane

Patent metadata

Field	Value
Publication number	US-9765032-B2
Application number	US-201415117058-A
Country	US
Kind code	B2
Filing date	Dec 26, 2014
Priority date	Feb 7, 2014
Publication date	Sep 19, 2017
Grant date	Sep 19, 2017

Abstract

A method for producing (R)-1,1,3-trimethyl-4-aminoindane includes the following steps (A), (B), and (C). Step (A) is a step of optically resolving 1,1,3-trimethyl-4-aminoindane to obtain (R)-1,1,3-trimethyl-4-aminoindane and (S)-1,1,3-trimethyl-4-aminoindane, step (B) is a step of racemizing the (S)-1,1,3-trimethyl-4-aminoindane obtained in the step (A) or (C) to obtain 1,1,3-trimethyl-4-aminoindane, and step (C) is a step of optically resolving the 1,1,3-trimethyl-4-aminoindane obtained in the step (B) to obtain (R)-1,1,3-trimethyl-4-aminoindane and (S)-1,1,3-trimethyl-4-aminoindane.

First claim

The invention claimed is:

1. A method for producing (R)-1,1,3-trimethyl-4-aminoindane, comprising the following steps (A), (B), and (C):
(A): a step of optically resolving 1,1,3-trimethyl-4-aminoindane to obtain (R)-1,1,3-trimethyl-4-aminoindane and (S)-1,1,3-trimethyl-4-aminoindane;
(B): a step of racemizing the (S)-1,1,3-trimethyl-4-aminoindane obtained in the step (A) or (C) to obtain 1,1,3-trimethyl-4-aminoindane; and
(C): a step of optically resolving the 1,1,3-trimethyl-4-aminoindane obtained in the step (B) to obtain (R)-1,1,3-trimethyl-4-aminoindane and (S)-1,1,3-trimethyl-4-aminoindane.

2. The production method according to claim 1 , wherein the steps (B) and (C) are repeated.

3. The production method according to claim 1 , wherein the step (C) is a step of optically resolving the 1,1,3-trimethyl-4-aminoindane obtained in the step (B) and the 1,1,3-trimethyl-4-aminoindane obtained in a step other than the step (B) to obtain (R)-1,1,3-trimethyl-4-aminoindane.

4. The production method according to claim 1 , comprising the following steps (A), (B′), (D), and (E):
(A): a step of optically resolving 1,1,3-trimethyl-4-aminoindane to obtain (R)-1,1,3-trimethyl-4-aminoindane and (S)-1,1,3-trimethyl-4-aminoindane;
(B′): a step of racemizing the (S)-1,1,3-trimethyl-4-aminoindane obtained in the step (A) or (E) to obtain 1,1,3-trimethyl-4-aminoindane;
(D): a step of purifying the 1,1,3-trimethyl-4-aminoindane obtained in the step (B′); and
(E): a step of optically resolving the 1,1,3-trimethyl-4-aminoindane obtained in the step (D) to obtain (R)-1,1,3-trimethyl-4-aminoindane and (S)-1,1,3-trimethyl-4-aminoindane.

5. The production method according to claim 4 , wherein the steps (B′), (D), and (E) are repeated.

6. The production method according to claim 1 , wherein the step (B) or (B′) is a step of bringing the (S)-1,1,3-trimethyl-4-aminoindane obtained in the step (A) into contact with a transition metal catalyst to perforin racemization.

7. The production method according to claim 1 , wherein the step (A) is a step comprising the following steps (A1), (A2), (A3), and (A4):
(A1): a step of mixing 1,1,3-trimethyl-4-aminoindane with D-tartaric acid and methanol to obtain a mixture including a methanol solvate of D-tartrate of (R)-1,1,3-trimethyl-4-aminoindane and D-tartrate of (S)-1,1,3-trimethyl-4-aminoindane;
(A2): a step of separating a solution containing D-tartrate of (S)-1,1,3-trimethyl-4-aminoindane and the methanol solvate of D-tartrate of (R)-1,1,3-trimethyl-4-aminoindane from the mixture obtained in the step (A1);
(A3): a step of mixing the methanol solvate of D-tartrate of (R)-1,1,3-trimethyl-4-aminoindane obtained in the step (A2) and an aqueous alkali metal hydroxide solution or aqueous alkali metal carbonate solution to obtain (R)-1,1,3-trimethyl-4-aminoindane; and
(A4): a step of mixing the solution including the D-tartrate of (S)-1,1,3-trimethyl-4-aminoindan obtained in the step (A2) and an aqueous alkali metal hydroxide solution or aqueous alkali metal carbonate solution to obtain (S)-1,1,3-trimethyl-4-aminoindane.

8. The production method according to claim 7 , wherein water is mixed into the reaction system prior to the step (A2).

9. The production method according to claim 4 , wherein the step (D) is a step comprising the following steps (D1), (D2), (D3), and (D4):
(D1): a step of reacting the 1,1,3-trimethyl-4-aminoindane obtained in the step (B′) with hydrogen hydride in the presence of water and a water-insoluble organic solvent;
(D2): a step of separating a layer dissolving therein a hydrogen halide salt of 1,1,3-trimethyl-4-aminoindane included in the mixture obtained in the step (D1) from other layer;
(D3): a step of precipitating the hydrogen halide salt of 1,1,3-trimethyl-4-aminoindane from the layer dissolving therein the hydrogen halide salt of 1,1,3-trimethyl-4-aminoindane obtained in the step (D2); and
(D4): a step of withdrawing the hydrogen halide salt of 1,1,3-trimethyl-4-aminoindane obtained in the step (D3) and reacting thus obtained hydrogen halide salt with a base.

10. The production method according to claim 9 , wherein the hydrogen halide is hydrogen chloride.

11. A method for producing a compound represented by the following formula (1):

wherein R 1 and R 2 each independently represent an alkyl group which may be substituted with a halogen atom, or a hydrogen atom), comprising the following steps (A), (B), (C), and (F):
(A): a step of optically resolving 1,1,3-trimethyl-4-aminoindane to obtain (R)-1,1,3-trimethyl-4-aminoindane and (S)-1,1,3-trimethyl-4-aminoindane;
(B): a step of racemizing the (S)-1,1,3-trimethyl-4-aminoindane obtained in the step (A) or (C) to obtain 1,1,3-trimethyl-4-aminoindane;
(C): a step of optically resolving the 1,1,3-trimethyl-4-aminoindane obtained in the step (B) to obtain (R)-1,1,3-trimethyl-4-aminoindane and (S)-1,1,3-trimethyl-4-aminoindane; and
(F): a step of reacting the (R)-1,1,3-trimethyl-4-aminoindane obtained in the step (C) with a compound represented by the formula (2) to obtain a compound represented by the formula (1):

wherein R 1 and R 2 represent the same meanings as above, and R 3 represents a halogen atom, a hydroxyl group, or an alkoxy group which may be substituted with a halogen atom.

12. A method for producing a compound represented by the following formula (1):

wherein R 1 and R 2 each independently represent an alkyl group which may be substituted with a halogen atom, or a hydrogen atom), comprising the following steps (A), (B), (C), (G), and (H):
(A): a step of optically resolving 1,1,3-trimethyl-4-aminoindane to obtain (R)-1,1,3-trimethyl-4-aminoindane and (S)-1,1,3-trimethyl-4-aminoindane;
(B): a step of racemizing the (S)-1,1,3-trimethyl-4-aminoindane obtained in the step (A) or (C) to obtain 1,1,3-trimethyl-4-aminoindane;
(C): a step of optically resolving the 1,1,3-trimethyl-4-aminoindane obtained in the step (B) to obtain (R)-1,1,3-trimethyl-4-aminoindane and (S)-1,1,3-trimethyl-4-aminoindane;
(G): a step of obtaining a compound represented by the formula (4) from a compound represented by the formula (3):

wherein R 1 and R 2 represent the same meanings as above

wherein R 1 and R 2 represent the same meanings as above; and
(H): a step of reacting the compound represented by the formula (4) obtained in the step (G) with the (R)-1,1,3-trimethyl-4-aminoindane obtained in the step (C) in the presence of a base to obtain the compound represented by the formula (1).

13. The production method according to claim 11 , wherein R 1 is a hydrogen atom or a methyl group, and R 2 is a methyl group, a monofluoromethyl group, a difluoromethyl group, or a trifluoromethyl group.

Assignees

• Sumitomo Chemical Co

Inventors

• Matsunaga Tadafumi
• Hiraguri Natsuru
• Takahashi Tomoaki
• Inui Tomohiko
• Tanimoto Masaya

Classifications

• C07D231/12

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• C07D231/16

  Halogen atoms or nitro radicals · CPC title

• C07C211/60

  containing a ring other than a six-membered aromatic ring forming part of at least one of the condensed ring systems · CPC title

• C07C209/88

  Separation of optical isomers · CPC title

• C07D231/10 Primary

  having two or three double bonds between ring members or between ring members and non-ring members · CPC title