Dimethylformamide → HCID 68605047, compound

HRID 448903Notes

Reaction equation

HRID 448903 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

5

Reactant 4

HCID 6228Dimethylformamide2×HCID 80641,4-ButanediolHCID 24758Sodium hydrideHCID 68602705HCID 68602705, compound

Product 1

HCID 68605047HCID 68605047, compound

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

  1. temperatureThe mixture was then heated at 50° C. for 2 hrs
  2. temperaturecooled to room temperature
  3. custompartitioned between DCM and water
  4. customThe organic layer was separated
  5. washwashed with 1H HCl
  6. dry with materialdried over Na2SO4
  7. concentrationThe filtrate was concentrated
  8. customthe residue purified

Sources & evidence

ORD record
ord-f5f0a8424d264a0d917d11c212ded338
Source dataset
uspto-grants-2013_07
Patent number
US08481738B2

Reaction notes

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