Sodium hydride → 4'-[(2-butyl-1H-thieno[3,4-d]imidazol-1-yl)methyl][1,1'-biphenyl]-2-carboxylic acid t-butyl ester

HRID 274614Notes

Reaction equation

HRID 274614 reaction equation
[CH2:1]([C:5]1[NH:9][C:8]2=[CH:10][S:11][CH:12]=[C:7]2[N:6]=1)[CH2:2][CH2:3][CH3:4].[H-].[Na+].[C:15]([O:19][C:20]([C:22]1[C:23]([C:28]2[CH:33]=[CH:32][C:31]([CH2:34]Br)=[CH:30][CH:29]=2)=[CH:24][CH:25]=[CH:26][CH:27]=1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>CN(C=O)C.[Cl-].[Na+].O>[C:15]([O:19][C:20]([C:22]1[C:23]([C:28]2[CH:33]=[CH:32][C:31]([CH2:34][N:9]3[C:8]4=[CH:10][S:11][CH:12]=[C:7]4[N:6]=[C:5]3[CH2:1][CH2:2][CH2:3][CH3:4])=[CH:30][CH:29]=2)=[CH:24][CH:25]=[CH:26][CH:27]=1)=[O:21])([CH3:18])([CH3:17])[CH3:16]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 9906257tert-Butyl 4'-(bromomethyl)biphenyl-2-carboxylateHCID 193706342-butyl-1H-thieno[3,4-d]imidazole

Product 1

HCID 538482894'-[(2-butyl-1H-thieno[3,4-d]imidazol-1-yl)methyl][1,1'-biphenyl]-2-carboxylic acid t-butyl esterYield 68%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a stirred solution of 2-butyl-1H-thieno-[3,4-d]imidazole (38 mg, 0.211 mmol) in DMF (1.6 mL) at room temperature was added NaH (316 mmol). After 30 minutes, tert-butyl-4'-bromomethylbiphenyl-2-carboxylate (80.5 mg, 0.232 mmol) was added in one portion. The reaction mixture was stirred for 2 hours and brine (5 mL) was added. Extractive workup (EtOAc) and purification by flash chromatography (SiO2, 40% EtOAc/hexane) gave 64 mg (68%) of 4'-[(2-butyl-1H-thieno[3,4-d]imidazol-1-yl)methyl][1,1'-biphenyl]-2-carboxylic acid t-butyl ester as a thick oil: 1H NMR (300 MHz, CDCl3) δ 7.78 (dd, 1H, J=7.5 and 1 Hz), 7.48 (td, 1H J=7.5 and 1 Hz), 7.40 (td, 1H, J=7.5 and 1 Hz) 7.32-7.26 (m, 3H), 7.19 (d, 2H, J=8 Hz), 6.99 (d, 1H, J=2.5 Hz), 6.28 (d, 1H, J=2.5 Hz), 5.17 (s, 2H), 2.78 (t, 2H, J=8 Hz), 1.91-1.81 (m, 2H), 1.54-1.41 (m, 2H), 1.23 (s, 9H), 0.96 (t, 3H, J=7 Hz).

Workup

  1. customExtractive workup (EtOAc) and purification by flash chromatography (SiO2, 40% EtOAc/hexane)

Sources & evidence

ORD record
ord-5c7f0d55cc824691ad04c0ea03fd70df
Source dataset
uspto-grants-1995_02
Patent number
US05389660

Reaction notes

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