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

HRID 2405861Notes

Reaction equation

HRID 2405861 reaction equation
[H-].[Na+].[C:3]([O:7][C:8](=[O:20])[NH:9][C:10]1[S:14][C:13]2[CH:15]=[CH:16][CH:17]=[CH:18][C:12]=2[C:11]=1[CH3:19])([CH3:6])([CH3:5])[CH3:4].[F:21][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][C:29]=1[F:30])[CH2:25]Br>CN(C=O)C.O>[C:3]([O:7][C:8](=[O:20])[N:9]([CH2:25][C:24]1[CH:27]=[CH:28][C:29]([F:30])=[C:22]([F:21])[CH:23]=1)[C:10]1[S:14][C:13]2[CH:15]=[CH:16][CH:17]=[CH:18][C:12]=2[C:11]=1[CH3:19])([CH3:6])([CH3:5])[CH3:4]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 5814364-(Bromomethyl)-1,2-difluorobenzeneHCID 57920379Tert-butyl-3-methylbenzo[b]thiophen-2-ylcarbamate

Product 1

HCID 57920462(3,4-Difluoro-benzyl)-(3-methyl-benzo[b]thiophen-2-yl)-carbamic acid tert-butyl esterYield 84%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60%, 0.37 g, 9.19 mmol) was added to a solution of compound 125-B (2.2 g, 8.35 mmol) in DMF (30 mL), at 0° C. and the resultant mixture was stirred for 15 minutes. 3,4-Difluorobenzylbromide (1.18 mL, 9.2 mmol) was added, and the solution was stirred at ambient temperature for 2 h. The reaction mixture was diluted with water, extracted with ethyl acetate, the organic extract washed with water (3×), brine, dried over sodium sulfate, filtered, and the solvent evaporated in vacuo. The crude residue was purified by flash column chromatography, eluting with an ethyl acetate-heptane gradient, to afford compound 125-C as an oil (2.73 g, 84%). 1H-NMR (CDCl3): δ 1.40 (s, 9H), 1.97 (s, 3H), 4.72 (s, 2H), 6.93-7.19 (m, 3H), 7.28-7.39 (m, 2H), 7.61 (d, 1H), 7.70 (d, 1H).

Workup

  1. extractionextracted with ethyl acetate
  2. extractionthe organic extract
  3. washwashed with water (3×), brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvent evaporated in vacuo
  7. customThe crude residue was purified by flash column chromatography
  8. washeluting with an ethyl acetate-heptane gradient

Sources & evidence

ORD record
ord-ff57217e83fe4c8e812e29dcca5a44af
Source dataset
uspto-grants-2014_08
Patent number
US08809327B2

Reaction notes

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