Diisopropylamine → methyl 3-[2-n-butyl-1-{(2-chlorophenyl)methyl}-1H-benzimidazol-7-yl]-3-hydroxy-2-(2-thienyl)methylpropanoate

HRID 487193Notes

Reaction equation

HRID 487193 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[S:13]1[CH:17]=[CH:16][CH:15]=[C:14]1[CH2:18][CH2:19][C:20]([O:22][CH3:23])=[O:21].[CH2:24]([C:28]1[N:32]([CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[Cl:40])[C:31]2[C:41]([CH:45]=[O:46])=[CH:42][CH:43]=[CH:44][C:30]=2[N:29]=1)[CH2:25][CH2:26][CH3:27]>O1CCCC1>[CH2:24]([C:28]1[N:32]([CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[Cl:40])[C:31]2[C:41]([CH:45]([OH:46])[CH:19]([CH2:18][C:14]3[S:13][CH:17]=[CH:16][CH:15]=3)[C:20]([O:22][CH3:23])=[O:21])=[CH:42][CH:43]=[CH:44][C:30]=2[N:29]=1)[CH2:25][CH2:26][CH3:27]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 566367Methyl 3-(thiophen-2-yl)propanoateHCID 190942612-n-butyl-1-(2-chlorophenyl)methyl-1H-benzimidazole-7-carboxaldehydeHCID 178418339Butyllithium

Product 1

HCID 19094218methyl 3-[2-n-butyl-1-{(2-chlorophenyl)methyl}-1H-benzimidazol-7-yl]-3-hydroxy-2-(2-thienyl)methylpropanoateYield 56.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of n-butyl lithium (0.4 mL of 2.5M in hexane, 1 mmol) in dry tetrahydrofuran (5 mL) at -78° C. under argon was treated with diisopropylamine (108 mg, 1.06 mmol). This mixture was stirred 10 minutes at -78° C. and methyl 3-(2-thienyl)propanoate (156 mg, 0.92 mmol) was added in tetrahydrofuran. After being stirred an additional 30 minutes at -78° C., a solution of 2-n-butyl-1-(2-chlorophenyl)methyl-1H-benzimidazole-7-carboxaldehyde (200 mg, 0.61 mmol) in tetrahydrofuran (1.5 mL) was added. This mixture was stirred at -78° C. for 15 minutes and the reaction was quenched with saturated ammonium chloride. The product was extracted into ethyl acetate, washed with water, dried and concentrated product was flash chromatographed over silica gel with 5-10% of methanol in ethyl acetate to provide 0.17 g (56%) of methyl 3-[2-n-butyl-1-{(2-chlorophenyl)methyl}-1H-benzimidazol-7-yl]-3-hydroxy-2-(2-thienyl)methylpropanoate as an oil.

Workup

  1. stirringAfter being stirred an additional 30 minutes at -78° C.
  2. stirringThis mixture was stirred at -78° C. for 15 minutes
  3. customthe reaction was quenched with saturated ammonium chloride
  4. extractionThe product was extracted into ethyl acetate
  5. washwashed with water
  6. customdried
  7. customchromatographed over silica gel with 5-10% of methanol in ethyl acetate

Sources & evidence

ORD record
ord-58fd245b859049c7bf7c01cc1420c5a2
Source dataset
uspto-grants-1994_03
Patent number
US05294631

Reaction notes

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