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

HRID 1008962Notes

Reaction equation

HRID 1008962 reaction equation
[CH:1]1([C:7]2[C:8]3[S:14][C:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[CH:12][C:9]=3[NH:10][CH:11]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Br[CH2:25][C:26]([O:28][CH3:29])=[O:27]>CN(C=O)C.CCOC(C)=O>[CH:1]1([C:7]2[C:8]3[S:14][C:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[CH:12][C:9]=3[N:10]([CH2:25][C:26]([O:28][CH3:29])=[O:27])[CH:11]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 67298608tert-butyl 6-cyclohexyl-4H-thieno[3,2-b]pyrrole-2-carboxylate

Product 1

HCID 67298619tert-butyl 6-cyclohexyl-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylateYield 85%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

tert-Butyl 6-cyclohexyl-4H-thieno[3,2-b]pyrrole-2-carboxylate (1 eq., from Step 1) was dissolved in anhydrous DMF (0.42 M) and sodium hydride (2 eq, 60% suspension in mineral oil) was added. The resulting suspension was stirred at RT for 30 min. Methyl bromoacetate (3 eq.) was then added and the solution was stirred at 50° C. for 1 h. After cooling down, the reaction mixture was diluted with EtOAc and washed sequentially with 1 N hydrochloric acid, saturated NaHCO3 solution and brine, dried over sodium sulfate and evaporated in vacuo. Purification by flash chromatography (PE:EtOAc, 9:1) afforded the title compound (85%). 1H-NMR (400 MHz, DMSO-d6, 300 K, δ) 7.72 (s, 1H), 7.06 (s, 1H), 5.05 (s, 2H), 3.69 (s, 3H), 2.56-2.50 (m, 1H), 1.99-1.67 (m, 5H), 1.52 (s, 9H), 1.43-1.19 (m, 5H). MS (ES+) m/z: 378 [M+H]+.

Workup

  1. stirringthe solution was stirred at 50° C. for 1 h
  2. temperatureAfter cooling down
  3. washwashed sequentially with 1 N hydrochloric acid, saturated NaHCO3 solution and brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated in vacuo
  6. customPurification by flash chromatography (PE:EtOAc, 9:1)

Sources & evidence

ORD record
ord-16406c297002434b8e42f0e7c09a0ef1
Source dataset
uspto-grants-2011_07
Patent number
US07973026B2

Reaction notes

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