Dimethyl Sulfoxide → HCID 68681541, compound

HRID 2241529Notes

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-a010f32cc7c94fac9bcd017d771cef8e
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723325B2

Reaction notes

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