Methyl iodide → (2S,3S)-3-tert-butyldimethylsilanyloxy-2-methylpyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester
Reaction equation
[CH3:1][O:2][C:3]([C@@H:5]1[C@@H:9]([O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])[CH2:8][CH2:7][N:6]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[O:4].[Li+].[CH3:26]C([N-]C(C)C)C.IC>C1COCC1>[CH3:1][O:2][C:3]([C@:5]1([CH3:26])[C@@H:9]([O:10][Si:11]([C:14]([CH3:17])([CH3:15])[CH3:16])([CH3:13])[CH3:12])[CH2:8][CH2:7][N:6]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[O:4]Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
To a solution of compound 4A (898 mg, 2.50 mmol) in THF (10 mL) at −78° C. under nitrogen was added a 1.8 M solution of LDA (3.50 mL, 6.25 mmol) and the reaction was stirred at −78° C. for 1 h. Iodomethane (1.56 mL, 25.0 mmol) was added, and the mixture was stirred at −78° C. for 4 h. The reaction was quenched by adding EtOAc and water. The layers were separated and the aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were washed with saturated aqueous NaHCO3 and brine, then dried over MgSO4, filtered and concentrated. Purification via silica gel chromatography (0-15% EtOAc in hexane) provided compound 4B (276 mg).
Workup
- stirringthe mixture was stirred at −78° C. for 4 h
- customThe reaction was quenched
- additionby adding EtOAc and water
- customThe layers were separated
- extractionthe aqueous layer was extracted with EtOAc (3×20 mL)
- washThe combined organic layers were washed with saturated aqueous NaHCO3 and brine
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated
- customPurification via silica gel chromatography (0-15% EtOAc in hexane)
Sources & evidence
- ORD record
- ord-5ce9d2da5df0451f96f8d4ee533f1da0
- Source dataset
- uspto-grants-2009_12
- Patent number
- US07625923B2
Reaction notes
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