Imidazole → (2S,4R)-4-(tert-Butyl-diphenyl-silanyloxy)-1-(4-trifluoromethoxy-phenylcarbamoyl)-pyrrolidine-2-carboxylic acid methyl ester

HRID 455251Notes

Reaction equation

HRID 455251 reaction equation
[CH3:1][C:2]([Si:5](Cl)([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([CH3:4])[CH3:3].[CH3:19][O:20][C:21]([C@@H:23]1[CH2:27][C@@H:26]([OH:28])[CH2:25][N:24]1[C:29](=[O:42])[NH:30][C:31]1[CH:36]=[CH:35][C:34]([O:37][C:38]([F:41])([F:40])[F:39])=[CH:33][CH:32]=1)=[O:22].N1C=CN=C1.O>CN(C=O)C>[CH3:19][O:20][C:21]([C@@H:23]1[CH2:27][C@@H:26]([O:28][Si:5]([C:2]([CH3:4])([CH3:3])[CH3:1])([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH2:25][N:24]1[C:29](=[O:42])[NH:30][C:31]1[CH:32]=[CH:33][C:34]([O:37][C:38]([F:39])([F:40])[F:41])=[CH:35][CH:36]=1)=[O:22]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 94078tert-ButyldiphenylchlorosilaneHCID 70976012(2S,4R)-4-Hydroxy-1-(4-trifluoromethoxy-phenylcarbamoyl)-pyrrolidine-2-carboxylic acid methyl ester

Product 1

HCID 70975932(2S,4R)-4-(tert-Butyl-diphenyl-silanyloxy)-1-(4-trifluoromethoxy-phenylcarbamoyl)-pyrrolidine-2-carboxylic acid methyl esterYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

TBDPSCl (1.73 g, 6.3 mmol) was dropped into a solution of (2S,4R)-4-Hydroxy-1-(4-trifluoromethoxy-phenylcarbamoyl)-pyrrolidine-2-carboxylic acid methyl ester (1.0 g, 2.9 mmol) and imidazole (0.98 g, 14.4 mmol) in DMF (20 mL), the mixture was stirred at room temperature for 4 hours. Then the mixture was poured into water (50 mL), extracted with ethyl acetate (3×30 mL). The organic layers was combined, washed with water (2×30 mL), brine (30 mL), then dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether=1:5) to give compound 1.48 g (88%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 7.67-7.62 (m, 4H), 7.47-7.37 (m, 8H), 7.13 (d, 2H, J=8.7 Hz), 6.37 (s, 1H), 4.68-4.55 (m, 2H), 3.71 (s, 3H), 3.54-3.42 (m, 2H), 2.33-2.25 (m, 1H), 2.05-1.97 (m, 1H), 1.06 (s, 9H); LC-MS: 587.2 [M+1]+.

Workup

  1. extractionextracted with ethyl acetate (3×30 mL)
  2. washwashed with water (2×30 mL), brine (30 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether=1:5)

Sources & evidence

ORD record
ord-7ef29620a6b2483ca05462ddbfeecf9e
Source dataset
uspto-grants-2013_07
Patent number
US08497288B2

Reaction notes

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