4-[1-Hydroxy-5-(2-methylthiopyrimidin-4-yl)-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]piperidine-1-carboxylic acid benzyl ester → 4-[5-(2-Methylthiopyrimidin-4-yl)-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]piperidine-1-carboxylic acid benzyl ester

HRID 342689Notes

Reaction equation

HRID 342689 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[N:18](O)[C:19]([C:32]3[CH:37]=[CH:36][N:35]=[C:34]([S:38][CH3:39])[N:33]=3)=[C:20]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=3)[N:21]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>CO.[Cl-].[Ti+3].[Cl-].[Cl-]>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[NH:18][C:19]([C:32]3[CH:37]=[CH:36][N:35]=[C:34]([S:38][CH3:39])[N:33]=3)=[C:20]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:30])([F:29])[F:31])[CH:23]=3)[N:21]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 1

HCID 107693624-[1-Hydroxy-5-(2-methylthiopyrimidin-4-yl)-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]piperidine-1-carboxylic acid benzyl ester

Product 1

HCID 106503634-[5-(2-Methylthiopyrimidin-4-yl)-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]piperidine-1-carboxylic acid benzyl esterYield 78.6%

Reagents, catalysts & solvents 2

HCID 10313229titanium(III) trichlorideCatalystHCID 887MethanolSolvent

Procedure

To a stirring solution of 4-[1-hydroxy-5-(2-methylthiopyrimidin-4-yl)-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]piperidine-1-carboxylic acid benzyl ester (9.5 g. crude, 0.0146 mole) in methanol (130 mL) at 20° C. was added titanium (III) chloride (25 mL, 0.029 mole, 15% wt in 20-30% HCl) dropwise over 10 minutes. The reaction was allowed to stir for 3 hours then quenched by pouring slowly into a mixture of 10% aqueous sodium bicarbonate (1.5 L) and ethyl acetate (600 mL). After stirring for 30 minutes the organic layer was removed and aqueous extract washed with ethyl acetate (2×200 mL). The organic extracts were combined, dried over anhydrous sodium sulfate, and concentrated to an oil. The oil was chromatographed on silica using 60% ethyl acetate/hexane to give 6.35 g of a yellow foam upon concentration of product containing fractions.

Workup

  1. customthen quenched
  2. additionby pouring slowly into a mixture of 10% aqueous sodium bicarbonate (1.5 L) and ethyl acetate (600 mL)
  3. stirringAfter stirring for 30 minutes the organic layer
  4. customwas removed
  5. extractionaqueous extract
  6. washwashed with ethyl acetate (2×200 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated to an oil
  9. customThe oil was chromatographed on silica using 60% ethyl acetate/hexane

Sources & evidence

ORD record
ord-a9cd2e6d3d54448e80bef2640fe82970
Source dataset
uspto-grants-1999_01
Patent number
US05859041

Reaction notes

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