Process for preparation of amino alcohols

Patent metadata

Field	Value
Publication number	US-11512040-B2
Application number	US-201917257080-A
Country	US
Kind code	B2
Filing date	Jul 2, 2019
Priority date	Jul 2, 2018
Publication date	Nov 29, 2022
Grant date	Nov 29, 2022

Abstract

A process for the preparation of amino alcohols includes condensing a compound of Formula (II), a stereoisomer, a tautomer, or a salt thereof with a compound of Formula (IIIa) or Formula (IIIb), a stereoisomer, a tautomer, or a salt thereof to form a condensation product; hydroxylating or acyloxylating the condensation product in the presence of an oxidant to obtain a hydroxylation or acyloxylation product; and subjecting the hydroxylation or acyloxylation product to one or more subsequent reactions comprising a hydrolysis reaction, alcohol deprotection, an amino lysis reaction, or a combination of two or more thereof to obtain an amino alcohol of Formula (I).

First claim

What is claimed is:

1. A process for the preparation of an amino alcohol, the process comprising:
condensing a compound of Formula (II), a stereoisomer, a tautomer, or a salt thereof with a compound of Formula (IIIa) or Formula (IIIb), a stereoisomer, a tautomer, or a salt thereof to form a condensation product;
hydroxylating or acyloxylating the condensation product in the presence of an oxidant to obtain a hydroxylation or acyloxylation product; and
subjecting the hydroxylation or acyloxylation product to one or more subsequent reactions comprising a hydrolysis reaction, an aminolysis reaction, alcohol deprotection, or a combination of two or more thereof to obtain an amino alcohol of Formula (I);
wherein:

L is a carbonyl, imine, acetal, or hemiacetal;
X is an amine or a protected amine;
R 1 , R 2 , R 3 , and R 4 are each independently a hydrogen, a substituted or unsubstituted C 1 -C 10 alkyl, a substituted or unsubstituted C 3 -C 10 cycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted heteroaryl, or two or more of R 1 , R 2 , R 3 , and R 4 together with the atoms to which they are attached form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aromatic, or substituted or unsubstituted heteroaromatic ring;
R 5 is a hydrogen, a halogen, a hydroxyl, an alkoxy, an O-acyl, a substituted or unsubstituted C 1 -C 10 alkyl, a substituted or unsubstituted C 3 -C 10 cycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heterocyclyl, or a substituted or unsubstituted heteroaryl;
R 6 is a hydrogen, a substituted or unsubstituted C 1 -C 10 alkyl, a substituted or unsubstituted C 3 -C 10 cycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heterocyclyl, or a substituted or unsubstituted heteroaryl;
R 7 and R 8 in Formula (IIIa) are each independently a hydrogen, a substituted or unsubstituted C 1 -C 10 alkyl, a substituted or unsubstituted C 3 -C 10 cycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted heteroaryl, or R 7 and R 8 together with the atoms to which they are attached form a substituted or unsubstituted aromatic or heteroaromatic ring; and
R 7a , R 7b , R 8a , and R 8b in Formula (IIIb) are each independently a hydrogen, a substituted or unsubstituted C 1 -C 10 alkyl, a substituted or unsubstituted C 3 -C 10 cycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted heteroaryl, or two or more of R 7a , R 7b , R 8a , and R 8b together with the atoms to which they are attached form a substituted or unsubstituted cycloalkyl or heterocyclyl ring.

2. The process of claim 1 , wherein R 1 is a substituted or unsubstituted C 1 -C 6 alkyl.

3. The process of claim 2 , wherein R 1 is selected from the group consisting of —CH 3 , —CH 2 CH 2 Ph, and —CH 2 C(CH 3 ) 3 .

4. The process of claim 1 , wherein R 2 is methyl.

5. The process of claim 1 , wherein R 3 and R 4 are each dependently hydrogen or a substituted or unsubstituted C 1 -C 6 alkyl.

6. The process of claim 1 , wherein the compound of Formula (II) is tert-butyl amine.

7. The process of claim 1 , wherein R 5 and R 6 are each independently hydrogen.

8. The process of claim 1 , wherein R 7 and R 8 in Formula (IIIa) together with the atoms to which they are attached form a C 5 -C 10 aromatic ring.

9. The process of claim 1 , wherein the compound of Formula (IIIa) is represented by a compound of Formula (V):

wherein:
L is a carbonyl, imine, acetal, or hemiacetal;
R 9 is hydrogen, halogen, hydroxyl, alkoxy, O-acyl;
R 10 , R 11 , R 12 , and R 13 are each independently a hydrogen, a halogen, an alkoxy, a substituted or unsubstituted C 1 -C 10 alkyl, a substituted or unsubstituted C 3 -C 10 cycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted heteroaryl, or two or more of R 10 , R 11 , R 12 and R 13 together with the atoms to which they are attached form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aromatic, or substituted or unsubstituted heteroaromatic ring;
R a1 , R b1 , R c1 , and R d1 are each independently a C—R′, N, or N + —R′,
wherein:
R′ is any one of R 10 , R 11 , R 12 and R 13 ; and
when any one of R a1 , R b1 , R c1 , and R d1 is N, the compound of Formula (V) does not include the corresponding R 10 , R 11 , R 12 and R 13 substituent.

10. The process of claim 1 , wherein L is a carbonyl and X is an amine.

11. The process of claim 10 , wherein X is —NH 2 .

12. The process of claim 1 , wherein L is C═NR e1 , wherein R e1 is hydrogen, a substituted or unsubstituted C 1 -C 10 alkyl, a substituted or unsubstituted C 3 -C 10 cycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heterocyclyl, or a substituted or unsubstituted heteroaryl.

13. The process of claim 9 , wherein R 10 , R 11 , R 12 and R 13 are each independently hydrogen.

14. The process of claim 9 , wherein at least one of R 10 , R 11 , R 12 and R 13 is an alkoxy, halogen, or C 1 -C 6 alkyl.

15. The process of claim 9 , wherein at least one of R 10 , R 11 , R 12 and R 13 are each independently hydrogen, and R a1 , R b1 , R c1 , and R d1 are each independently C—R′.

16. The process of claim 9 , wherein R 9 is hydrogen.

17. The process of claim 1 , wherein the compound of Formula (IIIa) is

18. The process of claim 1 , wherein the oxidant is selected from the group consisting of PhI(O(CO)R f1 ) 2 , PhI(OR f1 ) 2 , PhI(TFA) 2 , PhIO, 2-iodoxybenzoic acid (IBX), Dess-Martin periodinane, M 2 S 2 O 8 , R f1 COOI, R g1 OOR h1 , and O 2 ;
wherein:
R f1 is hydrogen, a C 1 -C 6 alkyl, or a substituted or unsubstituted aryl;
R g1 and R h1 are each independently a hydrogen, a C 1 -C 6 alkyl, or carboxyl group; and
M is an alkali metal.

19. The process of claim 1 , which is performed in the presence of a catalyst, and wherein said catalyst comprises palladium or a palladium salt.

20. The process of claim 1 , wherein the amino alcohol of Formula (I) is 2-amino-2-methylpropanol and the amine of Formula (II) is tert-butylamine.

Assignees

• Basf Se
• Basf Corp
• Univ California

Inventors

• Ernst Martin
• Zuend Stephan
• Su Bo
• Bunescu Ala
• Hartwig John F

Classifications

• C07C213/02 Primary

  by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups · CPC title

• C07C249/02

  of compounds containing imino groups · CPC title

• C07C213/00 Primary

  Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton · CPC title