Citric Acid → (R)-tert-butyl 3-(((methylsulfonyl)oxy)methyl)pyrrolidine-1-carboxylate
Reaction equation
[OH:1][CH2:2][C@@H:3]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4]1.C(N(CC)CC)C.[CH3:22][S:23](Cl)(=[O:25])=[O:24].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl>[CH3:22][S:23]([O:1][CH2:2][C@@H:3]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4]1)(=[O:25])=[O:24]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
A mixture of (R)-tert-butyl 3-(hydroxymethyl)pyrrolidine-1-carboxylate (21.5 g, 107 mmol) and triethylamine (30 mL, 214 mmol) in dichloromethane (250 mL) was cooled to 0° C. Methanesulfonyl chloride (12.5 mL, 160.5 mmol) was added dropwise via an addition funnel and the resulting mixture was stirred at 0° C. then gradually warmed to room temperature over 3 h. A 10% aqueous citric acid solution was added and the two layers were separated. The organic layer was washed with 10% aqueous citric acid, sat'd aqueous NaHCO3, and brine. The organic layer was dried over sodium sulfate, filtered and the solvent removed on a rotary evaporator to afford 30 g of (R)-tert-butyl 3-(((methylsulfonyl)oxy)methyl)pyrrolidine-1-carboxylate as an orange oil that was used without further purification. 1H NMR (400 MHz, DMSO-d6) δ 4.17 (m, 2H), 3.33 (m, 2H), 3.20 (m, 1H), 3.18 (s, 3H), 3.00 (m, 1H), 2.55 (m, 1H), 2.01 (m, 1H), 1.53 (m, 1H), 1.40 (s, 9H).
Workup
- temperaturethen gradually warmed to room temperature over 3 h
- customthe two layers were separated
- washThe organic layer was washed with 10% aqueous citric acid
- dry with materialThe organic layer was dried over sodium sulfate
- filtrationfiltered
- customthe solvent removed on a rotary evaporator
Sources & evidence
- ORD record
- ord-8230c727c2644725adc9eec6afa86aed
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09193714B2
Reaction notes
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