Stereoselective process

Patent metadata

Field	Value
Publication number	US-10189776-B2
Application number	US-201615758446-A
Country	US
Kind code	B2
Filing date	Sep 16, 2016
Priority date	Sep 18, 2015
Publication date	Jan 29, 2019
Grant date	Jan 29, 2019

Abstract

The invention relates to a method for the stereoselective preparation of compounds of formula (IV).

First claim

The invention claimed is:

1. A method for the preparation of a compound of formula (IV),

wherein
R 1a is NC—;
R 1b is H, CH 3 S—, Br, CH 3 SO 2 —;
A is NC—;
B is CH 3 ;
or A and B together with the carbon atoms to which they are attached form a ring selected from the group consisting of cyclopentenone, cyclohexenone and furanone;
R 2 is F 3 C—;
R 4 is

characterised in that the method comprises step (C), where step (C) is the stereoselective reaction of a compound of formula (I)

with a compound of formula (III)

wherein A, B, R 1a , R 1b , R 2 and R 4 have the meanings as defined above;
in the presence of an organo-catalyst of formula (X)

wherein
R 3 is selected from the group consisting of

2. The method according to claim 1 , for the preparation of compounds of formula (IV-A)

wherein a compound of formula (I-A)

is reacted with a compound of formula (III) in the presence of an organo-catalyst of formula (X);
wherein R 1a , R 1b , R 2 and R 4 have the meanings as defined above.

3. The method according to claim 1 , wherein R 3 of organo-catalyst of formula (X) is

4. The method according to claim 1 , wherein step (C) is carried out at a temperature from 0° C. to −70° C.

5. The method according to claim 1 , wherein step (C) is carried out in a solvent selected from the group consisting of ethyl acetate, Me-THF, THF, dichloromethane, isopropyl acetate, n-butyl acetate, toluene and DMF.

6. The method according to claim 1 , wherein step (C) is carried out using from 0.3 mol % to 10 mol % of the organo-catalyst of formula (X).

7. The method according to claim 1 , wherein step (C) is carried out using from 1.0 to 1.5 molar equivalents of the compound of formula (I).

8. The method according to claim 1 , wherein step (C) is carried out using 1.0 molar equivalents of compound of formula (III).

9. A method for the preparation of organo-catalyst of formula (X),

wherein R 3 is

characterised in that the method comprises a Suzuki-Miyaura coupling of unprotected 3,3′-dibromo-1,1-bi-2-napthol with 3,5-bis-(trifluoromethyl)phenyl boronic acid in the presence of palladium diacetate and a ligand of formula (Y)

Assignees

• Boehringer Ingelheim Int

Inventors

• Ries Uwe Joerg
• Haddad Nizar
• Qu Bo

Classifications

• C07F9/65744

  condensed with carbocyclic or heterocyclic rings or ring systems · CPC title

• B01J2231/34

  Other additions, e.g. Monsanto-type carbonylations, addition to 1,2-C=X or 1,2-C-X triplebonds, additions to 1,4-C=C-C=X or 1,4-C=-C-X triple bonds with X, e.g. O, S, NH/N · CPC title

• C07C2601/16

  the ring being unsaturated · CPC title

• C07C2601/10

  the ring being unsaturated · CPC title

• C07C269/06 Primary

  by reactions not involving the formation of carbamate groups · CPC title