Sodium hydride → HCID 68774932, compound

HRID 2261201Notes

Reaction equation

HRID 2261201 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:18])[C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[F:17])[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].[C:21]([O:25][C:26](=[O:29])[CH2:27]Br)([CH3:24])([CH3:23])[CH3:22]>CN(C=O)C.O.C(OCC)(=O)C.CC#N>[Br:1][C:2]1[CH:3]=[C:4]([N:8]([CH2:27][C:26]([O:25][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:29])[C:9](=[O:18])[C:10]2[C:11]([F:17])=[CH:12][CH:13]=[CH:14][C:15]=2[F:16])[CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 8713889HCID 8713889, compound

Product 1

HCID 68774932HCID 68774932, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of N-(3-bromophenyl)-2,6-difluorobenzamide in 200 mL of DMF at room temperature and under nitrogen atmosphere, NaH 60% in oil dispersion (104.7 mmol) is slowly added and the reaction mixture is stirred for 30 minutes. Tert-butylbromoacetate (104.7 mmol) is added and the reaction stirred at room temperature. After 12 hours the reaction is complete by TLC (hexanes:ethyl acetate=8:2) and analytical LCMS (20 to 100% CH3CN). Ethyl acetate and water are added to the reaction mixture and the phases are separated. The organic phase is dried on sodium sulfate, filtered and the solvent is evaporated. The crude is purified by automated column chromatography (gradient of hexanes and ethyl acetate) to give tert-butyl 2-(N-(3-bromophenyl)-2,6-difluorobenzamido)acetate: 1H NMR (400 MHz, CDCl3) δ 7.36 (bs, 1H), 7.20 (m, 1H), 7.07 (m, 2H), 6.96 (t, J=8 Hz, 1H), 6.62 (td, J=8 Hz, J2=1.2 Hz), 4.32 (s, 2H), 1.39 (s, 9H); MS: (ES+) 448.0 (M+23)+.

Workup

  1. stirringthe reaction stirred at room temperature
  2. customthe phases are separated
  3. customThe organic phase is dried on sodium sulfate
  4. filtrationfiltered
  5. customthe solvent is evaporated
  6. customThe crude is purified by automated column chromatography (gradient of hexanes and ethyl acetate)

Sources & evidence

ORD record
ord-ccae709e33004cea8f7c87c1bb7ef06d
Source dataset
uspto-grants-2010_12
Patent number
US07846949B2

Reaction notes

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