Methyl iodide → (4S)-1-tert-butyl 2-methyl 4-(tert-butyldimethylsilyloxy)-2-methylpyrrolidine-1,2-dicarboxylate
Reaction equation
[Li+].[CH3:2]C([N-]C(C)C)C.[Si:9]([O:16][C@@H:17]1[CH2:21][N:20]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@H:19]([C:29]([O:31][CH3:32])=[O:30])[CH2:18]1)([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10].CI>C1COCC1.CCOCC>[Si:9]([O:16][C@@H:17]1[CH2:21][N:20]([C:22]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:23])[C:19]([CH3:2])([C:29]([O:31][CH3:32])=[O:30])[CH2:18]1)([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:10])[CH3:11]Participants
6
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
LDA (2M in Heptane/THF/ethylbenzene, 48.5 ml, 97 mmol) was mixed with 100 ml THF at −78° C. and stirred for 5mins. (2S,4S)-1-tert-butyl 2-methyl 4-(tert-butyldimethylsilyloxy)pyrrolidine-1,2-dicarboxylate (14 g, 38.92 mmol) in 80 ml THF was added dropwise at −78° C. The mixture was stirred at −40° C. for 1 hr. Then the mixture was stirred at −78° C. for 10 mins. MeI (4.85 ml, 77.8 mmol) was slowly added and the mixture was stirred from −78° C. to r.t. overnight. The mixture was diluted with ether and quenched with 5% HCl. The organic layer was separated and washed with NaHCO3, brine, dried over MgSO4 and concentrated. 18.5 g of crude product as a diastereomeric mixture at C-2 was obtained.
Workup
- stirringThe mixture was stirred at −40° C. for 1 hr
- stirringThen the mixture was stirred at −78° C. for 10 mins
- stirringthe mixture was stirred from −78° C. to r.t. overnight
- customquenched with 5% HCl
- customThe organic layer was separated
- washwashed with NaHCO3, brine
- dry with materialdried over MgSO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-fa75206a470546e098acace4a0d28637
- Source dataset
- uspto-grants-2013_11
- Patent number
- US08592579B2
Reaction notes
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