Dimethyl Sulfoxide → 6-(2,3-Difluorophenyl)-5-fluoro-7,8-dihydro-5H-cyclohepta[b]pyridin-9(6H)-one

HRID 589008Notes

Reaction equation

C(Cl)(=O)C(Cl)=O.CS(C)=O.[F:11][C:12]1[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=1[CH:19]1[CH2:29][CH2:28][CH:27]([OH:30])[C:22]2=[N:23][CH:24]=[CH:25][CH:26]=[C:21]2[CH:20]1[F:31].C(N(CC)CC)C>ClCCl>[F:11][C:12]1[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=1[CH:19]1[CH2:29][CH2:28][C:27](=[O:30])[C:22]2=[N:23][CH:24]=[CH:25][CH:26]=[C:21]2[CH:20]1[F:31]

Participants

Conditions

Temperature: 23 °C

Procedure

To a solution of oxalyl chloride (1.2 g, 9.5 mmol) in dichloromethane (15 mL) at −65° C. was added DMSO (0.85 mL, 12 mmol), and the mixture was stirred for 30 min. A solution of 5R,6S,9R and 5S,6R,9S)-6-(2,3-difluorophenyl)-5-fluoro-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol (0.35 g, 1.9 mmol) in dichloromethane (3 mL) was added dropwise and the resulting solution was stirred at −65° C. for 30 min. After triethylamine (2.3 mL, 17 mmol) was added, the reaction mixture was gradually warmed to 23° C. over a period of 4 h, and then partitioned between water and dichloromethane. The organic layer was washed with water (3×), brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel, eluting with 50% ethyl acetate in petroleum ether to give the title compound as a racemic mixture. MS: m/z=292.2 (M+1).

Workup

stirringthe resulting solution was stirred at −65° C. for 30 min
custompartitioned between water and dichloromethane
washThe organic layer was washed with water (3×), brine
dry with materialdried over sodium sulfate
concentrationconcentrated in vacuo
customThe residue was purified by flash chromatography on silica gel
washeluting with 50% ethyl acetate in petroleum ether

Sources & evidence

ORD record: ord-c2aa790a4eaa46bda6f7f4f5f6e503fe
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09227973B2

Reaction notes

Loading…