Dimethyl malonate → (2S,4S)-N-allyloxycarbonyl-2-[2,2-bis(methoxycarbonyl)ethyl]-4-triphenylmethylthiopyrrolidine

HRID 1078705Notes

Reaction equation

HRID 1078705 reaction equation
[H-].[Na+].[C:3]([O:10][CH3:11])(=[O:9])[CH2:4][C:5]([O:7][CH3:8])=[O:6].[CH2:12]([O:15][C:16]([N:18]1[CH2:22][C@@H:21]([S:23][C:24]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:20][C@H:19]1[CH2:43]I)=[O:17])[CH:13]=[CH2:14].S([O-])(O)(=O)=O.[K+]>CN(C)C=O.O>[CH2:12]([O:15][C:16]([N:18]1[CH2:22][C@@H:21]([S:23][C:24]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:20][C@@H:19]1[CH2:43][CH:4]([C:3]([O:10][CH3:11])=[O:9])[C:5]([O:7][CH3:8])=[O:6])=[O:17])[CH:13]=[CH2:14]

Participants

7

Reactant 4

HCID 7943Dimethyl malonateHCID 24758Sodium hydrideHCID 516920Potassium bisulfateHCID 57112975(2S,4S)-N-allyloxycarbonyl-2-iodomethyl-4-tritylthiopyrrolidine

Product 1

HCID 57044475(2S,4S)-N-allyloxycarbonyl-2-[2,2-bis(methoxycarbonyl)ethyl]-4-triphenylmethylthiopyrrolidineYield 90.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To an ice-cooled suspension of sodium hydride (60%, in oil suspension, 300 mg, 7.5 mmol) in N,N-dimethylformamide (15 ml) was added dropwise dimethyl malonate (0.92 ml, 8.05 mmol) under a nitrogen atmosphere, and the mixture was stirred for 3.0 min at the same temperature. To the mixture was added a solution of (2S,4S)-N-allyloxycarbonyl-2-iodomethyl-4-triphenylmethylthiopyrrolidine (2.85 g, 5 mmol) in N,N-dimethylformamide (10 ml), and the mixture was stirred for 30 min under ice-cooling, for 1 h at room temperature, and then for 6 h at 60° C. The reaction mixture was poured into a mixture of water (30 ml) and 1N aqueous potassium hydrogensulfate (30 ml), and extracted with ethyl acetate (1×100 ml, 2×50 ml). The combined organic layer was washed successively with water and saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo, and the residue was subjected to silica gel column chromatography (hexane-ethyl acetate) to give (2S,4S)-N-allyloxycarbonyl-2-[2,2-bis(methoxycarbonyl)ethyl]-4-triphenylmethylthiopyrrolidine (2.59 g, yield: 90%).

Workup

  1. stirringthe mixture was stirred for 30 min under ice-
  2. waitfor 6 h at 60° C
  3. extractionextracted with ethyl acetate (1×100 ml, 2×50 ml)
  4. washThe combined organic layer was washed successively with water and saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-cf52248fa77c40e2841c4e0936b9db30
Source dataset
uspto-grants-1996_08
Patent number
US05550121

Reaction notes

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