Water → (6R,7aS)-6-(tert-Butyl-diphenyl-silanyloxy)-2-(4-trifluoromethoxy-phenyl)-hexahydro-pyrrolo[1,2-c]imidazol-3-one

HRID 455253Notes

Reaction equation

HRID 455253 reaction equation
CC([O-])(C)C.[K+].[F:7][C:8]([F:45])([F:44])[O:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]([N:19]2[CH2:23][C@H:22]([O:24][Si:25]([C:38]([CH3:41])([CH3:40])[CH3:39])([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:21][C@H:20]2[CH2:42]O)=[O:18])=[CH:12][CH:11]=1.S(Cl)(C1C=CC(C)=CC=1)(=O)=O.O>C1COCC1>[C:38]([Si:25]([C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)([C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[O:24][C@H:22]1[CH2:23][N:19]2[C:17](=[O:18])[N:16]([C:13]3[CH:14]=[CH:15][C:10]([O:9][C:8]([F:44])([F:45])[F:7])=[CH:11][CH:12]=3)[CH2:42][C@@H:20]2[CH2:21]1)([CH3:39])([CH3:41])[CH3:40]

Participants

6

Reactant 4

HCID 962WaterHCID 73974-Toluenesulfonyl chlorideHCID 23665647Potassium tert-butoxideHCID 71020558(2S,4R)-4-(tert-Butyl-diphenyl-silanyloxy)-2-hydroxymethyl-pyrrolidine-1-carboxylic acid (4-trifluoromethoxy-phenyl)-amide

Product 1

HCID 70975953(6R,7aS)-6-(tert-Butyl-diphenyl-silanyloxy)-2-(4-trifluoromethoxy-phenyl)-hexahydro-pyrrolo[1,2-c]imidazol-3-oneYield 83%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

t-BuOK (1.0 g, 8.9 mmol) was added to a solution of (2S,4R)-4-(tert-Butyl-diphenyl-silanyloxy)-2-hydroxymethyl-pyrrolidine-1-carboxylic acid (4-trifluoromethoxy-phenyl)-amide (2.0 g, 3.6 mmol) in anhydrous THF (50 mL) at 0° C. The mixture was stirred for 15 minutes at 0° C. Then tosyl-chloride (0.88 g, 4.6 mmol) was added to the mixture, and the mixture was stirred for 30 minutes at 0° C. The mixture was poured into water (50 mL), extracted with ethyl acetate (3×50 mL). The organic layers was combined, washed with brine (50 mL), dried over anhydrous sodium sulphate, filtered and concentrated. The residue was purified by silica-gel column chromatography (petroleum ether/ethyl acetate=10:1) to give 1.6 g (83%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 7.68-7.63 (m, 4H), 7.58 (d, 2H, J=9.3 Hz), 7.50-7.39 (m, 6H), 7.19 (d, 2H, J=9.0 Hz), 4.56 (t, 1H, J=5.1 Hz), 4.30-4.22 (m, 1H), 4.04 (t, 1H, J=8.4 Hz), 3.86 (dd, 1H, J1=12.6 Hz, J2=5.7), 3.67 (dd, 1H, J1=9.3 Hz, J2=2.4 Hz), 3.18 (d, 1H, J=12.6 Hz), 2.07 (dd, 1H, J1=12.6, J2=5.4), 1.46-1.37 (m, 1H), 1.11 (s, 9H).

Workup

  1. stirringthe mixture was stirred for 30 minutes at 0° C
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. washwashed with brine (50 mL)
  4. dry with materialdried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica-gel column chromatography (petroleum ether/ethyl acetate=10:1)

Sources & evidence

ORD record
ord-cee8be1bd29641328017a0bb095238be
Source dataset
uspto-grants-2013_07
Patent number
US08497288B2

Reaction notes

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