Dimethylformamide → HCID 68605047, compound
Reaction equation
[H-].[Na+].[CH2:3]([OH:8])[CH2:4][CH2:5][CH2:6][OH:7].[Br:9][C:10]1[C:11]([Cl:29])=[CH:12][C:13](F)=[C:14]([CH:27]=1)[C:15]([NH:17][C:18]1[C:23]([CH3:24])=[CH:22][CH:21]=[CH:20][C:19]=1[O:25][CH3:26])=[O:16].[CH3:30]N(C=O)C>>[Br:9][C:10]1[C:11]([Cl:29])=[CH:12][C:13]([O:7][CH2:6][CH2:5][CH2:4][CH2:3][OH:8])=[C:14]([CH:27]=1)[C:15]([N:17]([C:18]1[C:23]([CH3:24])=[CH:22][CH:21]=[CH:20][C:19]=1[O:25][CH3:26])[CH3:30])=[O:16]Participants
Procedure
NaH (373 mg, 9.3 mmol, 60% in mineral oil) was added to 1,4-butanediol (3.5 g, 38.9 mmol) in dry DMF (50 mL). The mixture was stirred at room temperature for 15 minutes. 5-Bromo-4-chloro-2-fluoro-N-(2-methoxy-6-methyl-phenyl)-benzamide (3.0 g, 7.8 mmol) in DMF (25 mL) was added slowly. The mixture was then heated at 50° C. for 2 hrs, cooled to room temperature and partitioned between DCM and water. The organic layer was separated, washed with 1H HCl, sat NaHCO3 and brine, then dried over Na2SO4. The filtrate was concentrated and the residue purified using column chromatography with a gradient of 50% ethyl acetate in hexanes to 100% ethyl acetate to yield 5-bromo-4-chloro-2-(4-hydroxy-butoxy)-N-(2-methoxy-6-methyl-phenyl)-N-methyl-benzamide (2.3 g). MS: 457.9 (M+H)+, tR=2.38 min (method 1).
Workup
- temperatureThe mixture was then heated at 50° C. for 2 hrs
- temperaturecooled to room temperature
- custompartitioned between DCM and water
- customThe organic layer was separated
- washwashed with 1H HCl
- dry with materialdried over Na2SO4
- concentrationThe filtrate was concentrated
- customthe residue purified
Sources & evidence
- ORD record
- ord-fba39201f80941419ae7c0b5eb4e4f96
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08952161B2
Reaction notes
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