Cesium carbonate → 4-{3-Chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-3-fluoro-benzonitrile

HRID 1095919Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1F)[C:5]#[N:6].C([O-])([O-])=O.[Cs+].[Cs+].[Cl:17][C:18]1[CH:19]=[C:20]([OH:39])[CH:21]=[CH:22][C:23]=1[CH:24]([CH3:38])[C:25]([C:31]1[CH:36]=[CH:35][N:34]=[C:33]([Cl:37])[CH:32]=1)([OH:30])[C:26]([F:29])([F:28])[F:27]>CN(C=O)C>[Cl:17][C:18]1[CH:19]=[C:20]([CH:21]=[CH:22][C:23]=1[CH:24]([CH3:38])[C:25]([C:31]1[CH:36]=[CH:35][N:34]=[C:33]([Cl:37])[CH:32]=1)([OH:30])[C:26]([F:29])([F:28])[F:27])[O:39][C:9]1[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[CH:3][C:2]=1[F:1]

Participants

Conditions

Temperature: 120 °C

Procedure

3,4-Difluorobenzonitrile (CAS Reg. No. 64248-62-0, 23 mg) and Cs2CO3 (13 mg) were added to a solution of 3-chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenol (Example 19 step 5, 50 mg) in DMF (1 ml). The mixture was heated to 120° C. for 30 min in a microwave oven. The mixture was purified by prep. HPLC (C18-column, solvent gradient 30-98% CH3CN in 0.1% HCOOH[aq]) to give the title compound (43 mg) as a white foam. MS (m/e)=485.2 [M+H+].

Workup

customThe mixture was purified by prep

Sources & evidence

ORD record: ord-58c78cef08874961bbc1bc9976c26dcb
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08138189B2

Reaction notes

Loading…