4-Chloroaniline → 1-(1,1-Dimethylethyl) 3-ethyl (3R,4R)-4-[[(4-chlorophenyl)amino]carbonyl]-1,3-pyrrolidinedicarboxylate
Reaction equation
[CH2:1]([O:3][C:4]([C@@H:6]1[C@@H:10]([C:11]([OH:13])=O)[CH2:9][N:8]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:7]1)=[O:5])[CH3:2].C(N(CC)C(C)C)(C)C.[Cl:30][C:31]1[CH:37]=[CH:36][C:34]([NH2:35])=[CH:33][CH:32]=1>C(#N)C>[CH2:1]([O:3][C:4]([C@@H:6]1[C@@H:10]([C:11](=[O:13])[NH:35][C:34]2[CH:36]=[CH:37][C:31]([Cl:30])=[CH:32][CH:33]=2)[CH2:9][N:8]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:7]1)=[O:5])[CH3:2]Participants
Conditions
- Temperature
- 0 °C
Procedure
Compound 7a (4.91 g; 17.1 mmol) is suspended in acetonitrile (25 ml) and N,N-diisopropyl ethyl amin (3.58 ml; 20.5 mmol) is added at 0° C. Bis(2-oxo-3-oxazolidinyl) phosphinic chloride BOP-Cl (5.22 g; 20.5 mmol) is added as a solid and after stirring for 30 min at 0° C. 4-chloroaniline (2.18 g; 17.1 mmol) is added to the reaction mixture. The mixture is stirred for 2 h at 0° C., evaporated to dryness and dissolved in ethyl acetate (ml). The organic phase is washed with 0.1 N HCl (2×ml), with saturated aquous Na2CO3 solution, water and brine and dried over Na2SO4. The organic phase is filtered and the filtrate is evaporated to dryness. The crude product is purified by silica gel chromatography. Yield: 4.7 g (69.3%), ESI-MS: m/z=395 [M−H]−, Cl-pattern
Workup
- stirringThe mixture is stirred for 2 h at 0° C.
- customevaporated to dryness
- dissolutiondissolved in ethyl acetate (ml)
- washThe organic phase is washed with 0.1 N HCl (2×ml), with saturated aquous Na2CO3 solution, water and brine
- dry with materialdried over Na2SO4
- filtrationThe organic phase is filtered
- customthe filtrate is evaporated to dryness
- customThe crude product is purified by silica gel chromatography
Sources & evidence
- ORD record
- ord-4d580022d8974e95be7cd62de4e41042
- Source dataset
- uspto-grants-2009_06
- Patent number
- US07550487B2
Reaction notes
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