Dimethyl Sulfoxide → HCID 68681541, compound

HRID 1820369Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]([F:15])([F:14])[F:13])[C:6]([C:16]([N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)=[O:17])=[CH:5]2.C1(P([C:47]2[CH:52]=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.[CH2:60]([OH:62])C.CS(C)=[O:65]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:52]([O:65][C:60]([C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]([F:13])([F:14])[F:15])[C:6]([C:16]([N:18]1[CH2:19][CH2:20][O:21][CH2:22][CH2:23]1)=[O:17])=[CH:5]2)=[O:62])[CH3:47]

Participants

Conditions

Temperature: 75 °C

Procedure

A mixture of [5-bromo-1-(2,2,2-trifluoro-ethyl)-1H-indol-2-yl]-morpholin-4-yl-methanone (1.49 g, 4 mmol), palladium acetate (171 mg, 0.76 mmol), 1,3-bis(diphenylphosphino)propane (346 mg, 0.84 mmol), triethylamine (0.58 mL, 4 mmol), ethanol (3 mL) and dimethylsulfoxide (3 mL) was flushed with carbon monoxide. The reaction mixture was stirred vigorously at 75° C. (oil bath), under carbon monoxide (1 Atm) for 19 h. The red mixture was diluted with ethyl acetate, filtered and partitioned between ethyl acetate and brine. The organic layer was washed with brine and dried in vacuo. The crude product was purified by flash chromatography on silica gel with dichloromethane:ethyl acetate (98:2 v/v) as eluant, to give 924 mg (63%) of the desired compound as an off-white solid.

Workup

customwas flushed with carbon monoxide
additionThe red mixture was diluted with ethyl acetate
filtrationfiltered
custompartitioned between ethyl acetate and brine
washThe organic layer was washed with brine
customdried in vacuo
customThe crude product was purified by flash chromatography on silica gel with dichloromethane:ethyl acetate (98:2 v/v) as eluant

Sources & evidence

ORD record: ord-199b359da3e74fd1a92684a2f853e31d
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07601711B2

Reaction notes

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