Sodium hydride → (4-Fluoro-3-trifluoromethyl-benzyl)-(3-methyl-benzo[b]thiophen-2-yl)-carbamic acid tert-butyl ester

HRID 589599Notes

Reaction equation

HRID 589599 reaction equation
[C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1[S:12][C:11]2[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=2[C:9]=1[CH3:17])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[F:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26]Br)=[CH:24][C:23]=1[C:30]([F:33])([F:32])[F:31]>CN(C=O)C>[C:1]([O:5][C:6](=[O:18])[N:7]([CH2:26][C:25]1[CH:28]=[CH:29][C:22]([F:21])=[C:23]([C:30]([F:33])([F:31])[F:32])[CH:24]=1)[C:8]1[S:12][C:11]2[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=2[C:9]=1[CH3:17])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27375774-Fluoro-3-(trifluoromethyl)benzyl bromideHCID 57920379Tert-butyl-3-methylbenzo[b]thiophen-2-ylcarbamate

Product 1

HCID 59376673(4-Fluoro-3-trifluoromethyl-benzyl)-(3-methyl-benzo[b]thiophen-2-yl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of compound 6-B (2.0 g, 7.59 mmol) in DMF (20 mL), cooled to 0° C., was added 60% NaH (0.334 g, 8.35 mmol) and the reaction mixture was stirred for 15 minutes. 4-Fluoro-3-trifluoromethyl benzyl bromide (1.26 mL, 8.35 mmol) was added drop-wise at 0° C. and the reaction mixture was stirred for 1 hour. The reaction mixture was poured into ice water, extracted with ethyl acetate, the organic phase washed with H2O, brine, dried over MgSO4, filtered, and the solvent evaporated under reduced pressure. The crude oil was purified by flash column chromatography (SiO2) eluting with a 0% EtOAc-heptane to 25% EtOAc-heptane gradient to afford compound 6-C as a clear oil. Compound 6-C was used without further purification in the next step.

Workup

  1. stirringthe reaction mixture was stirred for 1 hour
  2. extractionextracted with ethyl acetate
  3. washthe organic phase washed with H2O, brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customthe solvent evaporated under reduced pressure
  7. customThe crude oil was purified by flash column chromatography (SiO2)
  8. washeluting with a 0% EtOAc-heptane to 25% EtOAc-heptane gradient

Sources & evidence

ORD record
ord-686b4f8a31be4d319efdb01002f48a2f
Source dataset
uspto-grants-2016_01
Patent number
US09233947B2

Reaction notes

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