Diisopropylamine → methyl 3-[2-n-butyl-1-(2-chlorophenyl)methyl-1H-imidazol-5-yl]-3-hydroxy-2-(2-thienyl)methyl-propanoate

HRID 1646116Notes

Reaction equation

HRID 1646116 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[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:29]([CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[Cl:42])[C:30]([CH:33]=[O:34])=[CH:31][N:32]=1)[CH2:25][CH2:26][CH3:27]>O1CCCC1>[CH2:24]([C:28]1[N:29]([CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[Cl:42])[C:30]([CH:33]([OH:34])[CH:19]([CH2:18][C:14]2[S:13][CH:17]=[CH:16][CH:15]=2)[C:20]([O:22][CH3:23])=[O:21])=[CH:31][N:32]=1)[CH2:25][CH2:26][CH3:27]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 566367Methyl 3-(thiophen-2-yl)propanoateHCID 101075301H-Imidazole-5-carboxaldehyde, 2-butyl-1-[(2-chlorophenyl)methyl]-HCID 178418339Butyllithium

Product 1

HCID 10003731methyl 3-[2-n-butyl-1-(2-chlorophenyl)methyl-1H-imidazol-5-yl]-3-hydroxy-2-(2-thienyl)methyl-propanoateYield 81.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of diisopropylamine (1.96 g, 0.0194 mol) in dry tetrahydrofuran (40 mL) held at -78° C. under argon was added n-butyl lithium (7.3 mL, 0.0183 mol of 2.5M in toluene), and the mixture was stirred for 10 minutes. Then, methyl 3-(2-thienyl)propanoate (2.83 g, 0.0166 mol) in tetrahydrofuran (2 mL) was added, and the mixture was stirred for 30 minutes at -78° C. A solution of 2-n-butyl-1-(2-chlorophenyl)methyl-1H-imidazol-5-carboxaldehyde (3 g, 0.0111 mol) in tetrahydrofuran (4 mL) was added, and the resulting mixture was stirred at -78° C. for 30 minutes. The reaction was partitioned between saturated ammonium chloride solution and ether, the organic extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated to 6.67 g of crude product. This was flash chromatographed over 70 g of silica gel with 4:1 ethyl acetate/hexanes to provide 4.03 g (81%) of methyl 3-[2-n-butyl-1-(2-chlorophenyl)methyl-1H-imidazol-5-yl]-3-hydroxy-2-[(2-thienyl)methyl]propanoate.

Workup

  1. customheld at -78° C. under argon
  2. stirringthe mixture was stirred for 30 minutes at -78° C
  3. stirringthe resulting mixture was stirred at -78° C. for 30 minutes
  4. customThe reaction was partitioned between saturated ammonium chloride solution and ether
  5. extractionthe organic extract
  6. washwas washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated to 6.67 g of crude product
  9. customThis was flash chromatographed over 70 g of silica gel with 4:1 ethyl acetate/hexanes

Sources & evidence

ORD record
ord-54b9bbb9ddc54a13bcf4367526d34de1
Source dataset
uspto-grants-1993_01
Patent number
US05177096

Reaction notes

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