Vinyl chloroformate → 4-(4-Nitro-phenyl)-pyrrolidine-1,3-dicarboxylic acid 3-ethyl ester 1-vinyl ester
Reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[CH:10]([C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=2)[CH2:9][N:8](CC2C=CC=CC=2)[CH2:7]1)=[O:5])[CH3:2].Cl[C:28]([O:30][CH:31]=[CH2:32])=[O:29]>ClCCCl>[CH:31]([O:30][C:28]([N:8]1[CH2:9][CH:10]([C:11]2[CH:12]=[CH:13][C:14]([N+:17]([O-:19])=[O:18])=[CH:15][CH:16]=2)[CH:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:7]1)=[O:29])=[CH2:32]Participants
Procedure
A stirred solution of 1-benzyl-4-(4-nitro-phenyl)-pyrrolidine-3-carboxylic acid ethyl ester (9.56 g, Reference Example 6) in 1,2-dichloroethane (25 ml), at 25° C. and under an atmosphere of argon, was treated dropwise with vinyl chloroformate (2.5 ml). The resulting mixture was heated at reflux for 20 hours then evaporated (40° C. and 2.7 kPa). The residue was subjected to flash chromatography on silica (0.045-0.020 mm particle size) eluting with a mixture of cyclohexane and ethyl acetate (50:50, v/v) affording the title compound (8.38 g) as a white solid. 1H-NMR [500 MHz, (CD3)2SO]: δ 1.07 (m, 3H); 3.35 to 3.70 and 3.70 to 4.00 (2 m, 6H); 4.03 (m, 2H); 4.54 and 4.56 (2 d, J=6 Hz, 1H); 4.79 and 4.85 (2 d, J=14 Hz, 1H); 7.16 (dd, J=14 and 6 Hz, 1H); 7.69 (d, J=8 Hz, 2H); 8.23 (d, J=8 Hz, 2H). MS (EI): 334 [M]+.
Workup
- temperatureThe resulting mixture was heated
- temperatureat reflux for 20 hours
- customthen evaporated (40° C. and 2.7 kPa)
- washeluting with a mixture of cyclohexane and ethyl acetate (50:50
Sources & evidence
- ORD record
- ord-6a5c1125986944abaf806e99c1ffbfb3
- Source dataset
- uspto-grants-2003_04
- Patent number
- US06548533B2
Reaction notes
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