Sodium hydride → methyl 6-(2-fluorocyclohexyl)-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate

HRID 1008990Notes

Reaction equation

HRID 1008990 reaction equation
[H-].[Na+].[F:3][CH:4]1[CH2:9][CH2:8][CH2:7][CH2:6][CH:5]1[C:10]1[C:11]2[S:17][C:16]([C:18]([O:20][CH3:21])=[O:19])=[CH:15][C:12]=2[NH:13][CH:14]=1.Br[CH2:23][C:24]([O:26][CH3:27])=[O:25]>CN(C=O)C>[F:3][CH:4]1[CH2:9][CH2:8][CH2:7][CH2:6][CH:5]1[C:10]1[C:11]2[S:17][C:16]([C:18]([O:20][CH3:21])=[O:19])=[CH:15][C:12]=2[N:13]([CH2:23][C:24]([O:26][CH3:27])=[O:25])[CH:14]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 67298952methyl 6-(2-fluorocyclohexyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate

Product 1

HCID 67298580methyl 6-(2-fluorocyclohexyl)-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylateYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

60% NaH in mineral oil (2 eq.) was added at RT to a 0.25M solution of methyl 6-(2-fluorocyclohexyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate in dry DMF, after few min methyl bromoacetate (3 eq.) was added and the mixture was stirred at 60° C. for 1 h and left overnight at RT. After dilution with EtOAc, the organic layer was washed with 1N HCl, sat. NaHCO3 and brine, dried over Na2SO4 and concentrated. Chromatography (PE/EtOAc) afforded the title compound (53%). 1H-NMR (400 MHz, CDCl3, 300K, δ) 7.60 (s, 1H), 6.92 (s, 1H), 4.74 (s, 2H), 4.50 (dtd, 1H, J 48.9, 10.3, 4.5), 3.88 (s, 3H), 3.77 (s, 3H), 2.85-2.76 (m, 1H), 2.25-2.11 (m, 2H), 1.90-1.74 (m, 2H), 1.68-1.54 (m, 2H), 1.44-1.33 (m, 2H); MS (ES+) m/z 354 (M+H)+.

Workup

  1. waitleft overnight at RT
  2. washAfter dilution with EtOAc, the organic layer was washed with 1N HCl, sat. NaHCO3 and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-6ff7115524d648419cbb5c7b27d3e9cb
Source dataset
uspto-grants-2011_07
Patent number
US07973026B2

Reaction notes

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