Sodium hydride → HCID 68468561, compound

HRID 505800Notes

Reaction equation

HRID 505800 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH3:13])[C:11]3[C:14]([CH:21]4[O:25][CH2:24][CH2:23][O:22]4)=[C:15]([C:17]([O:19][CH3:20])=[O:18])[S:16][C:10]=3[C:9]=2[CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)=[CH:4][CH:3]=1.[H-].[Na+].BrC[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37]>CN(C=O)C>[C:39]([O:38][C:36](=[O:37])[CH2:13][N:12]1[C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[C:9]([CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)[C:10]2[S:16][C:15]([C:17]([O:19][CH3:20])=[O:18])=[C:14]([CH:21]3[O:25][CH2:24][CH2:23][O:22]3)[C:11]1=2)([CH3:42])([CH3:41])[CH3:40]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 68470999HCID 68470999, compound

Product 1

HCID 68468561HCID 68468561, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution (0.23 M) of methyl 5-(4-chlorophenyl)-6-cyclohexyl-3-(1,3-dioxolan-2-yl)-4-methyl-4H-thieno[3,2-b]pyrrole-2-carboxylate in DMF at 0° C. was treated with NaH (2 eq., 60% dispersion in mineral oil), and the suspension was stirred at RT for 30 min, then tert-butyl bromoacetate (4 eq.) was added. The reaction mixture was heated at 50° C. for 3.5 h then it was quenched by addition of aqueous NH4Cl (saturated solution) and diluted with Et2O. The aqueous phase was separated and extracted with Et2O. The combined organic phase was washed sequentially with aqueous HCl (1 N), aqueous NaHCO3 (saturated solution) and brine then dried and evaporated. The residue was purified by flash chromatography on silica gel (1:19 to 1:1 AcOEt/petroleum ether) to afford methyl 4-(2-tert-butoxy-2-oxoethyl)-5-(4-chlorophenyl)-6-cyclohexyl-3-(1,3-dioxolan-2-yl)-4H-thieno[3,2-b]pyrrole-2-carboxylate. This compound was dissolved in DCM and the resulting solution (0.1 M) was treated with TFA (16 eq.). The reaction was stirred at RT for 3 h then solvents were evaporated under reduced pressure and the residue was purified by flash chromatography on silica gel (1:99 to 1:19 MeOH/DCM) to afford the title compound (55%).

Workup

  1. temperatureThe reaction mixture was heated at 50° C. for 3.5 h
  2. customit was quenched by addition of aqueous NH4Cl (saturated solution)
  3. additiondiluted with Et2O
  4. customThe aqueous phase was separated
  5. extractionextracted with Et2O
  6. washThe combined organic phase was washed sequentially with aqueous HCl (1 N), aqueous NaHCO3 (saturated solution) and brine
  7. customthen dried
  8. customevaporated
  9. customThe residue was purified by flash chromatography on silica gel (1:19 to 1:1 AcOEt/petroleum ether)

Sources & evidence

ORD record
ord-a6d389b0d21741ee8a14ff9935cc3bfa
Source dataset
uspto-grants-2010_08
Patent number
US07781431B2

Reaction notes

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