N-(2,6-Difluoro-3-hydroxy-phenyl)-2-fluoro-3-(3-fluorophenyl)-5-methoxy-benzamide → 2,4-Difluoro-3-[[2-fluoro-3-(3-fluorophenyl)-5-methoxy-phenyl]methylamino]phenol

HRID 1771613Notes

Reaction equation

[F:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[C:4]([F:9])[C:3]=1[NH:10][C:11](=O)[C:12]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=2)[C:13]=1[F:27]>C1COCC1>[F:1][C:2]1[C:3]([NH:10][CH2:11][C:12]2[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=3)[C:13]=2[F:27])=[C:4]([F:9])[CH:5]=[CH:6][C:7]=1[OH:8]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of N-(2,6-difluoro-3-hydroxy-phenyl)-2-fluoro-3-(3-fluorophenyl)-5-methoxy-benzamide (300 mg, 0.77 mmol, 1.0 eq) in THF (10 mL) at 0° C. under N2 was added a solution of BH3 (1M in THF, 4 mL, 4.0 mmol, 5.2 eq) dropwise. The reaction mixture was heated to 60° C. and stirred for 1.5 h. The reaction was cooled to room temperature then quenched by addition of 1M HCl. The mixture was stirred at room temperature for 1.5 h, then extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:4) to give the title compound as a yellow oil (180 mg, 62%).

Workup

temperatureThe reaction was cooled to room temperature
customthen quenched by addition of 1M HCl
stirringThe mixture was stirred at room temperature for 1.5 h
extractionextracted with EtOAc
extractionThe organic extract
washwas washed with water and brine
dry with materialdried (Na2SO4)
filtrationfiltered
customevaporated in vacuo
customThe residue was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:4)

Sources & evidence

ORD record: ord-8de3ec2b629342419ba3376c3caf866c
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09249085B2

Reaction notes

Loading…