Reaction equation
[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.C(N(CC)CC)C.[CH3:21][S:22](Cl)(=[O:24])=[O:23]>C1(C)C=CC=CC=1>[CH3:21][S:22]([O:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1)(=[O:24])=[O:23]Participants
Conditions
- Temperature
- -15 °C
Procedure
To a solution of tert-butyl (R)-3-hydroxypyrrolidine-1-carboxylate (200 g, 1.07 mol) and triethylamine (167 g, 1.63 mol) in toluene (700 mL) at −20 to −30° C. was added methanesulfonyl chloride (156 g, 1.36 mol) drop-wise while maintaining the temperature at −10 to −20° C. The solution was warmed to ambient temperature and allowed to stir. The reaction solution was sampled hourly and analyzed by HPLC to establish completion of the reaction. Upon completion of the reaction, the suspension was filtered to remove the triethylamine hydrochloride. The filtrate was washed with ˜600 mL of dilute aqueous sodium bicarbonate solution. The organic layer was dried and concentrated under reduced pressure to give 2 as a viscous oil (260 g, 92%) which is used without further purification. 1H NMR (CDCl3, 400 MHz) δ 5.27 (m, 1H), 3.44-3.76 (m, 4H), 3.05 (s, 3H), 2.26 (m, 1H), 2.15 (m, 1H), 1.47 (s, 9H).
Workup
- temperatureThe solution was warmed to ambient temperature
- aliquotThe reaction solution was sampled hourly
- customcompletion of the reaction
- customUpon completion of the reaction
- filtrationthe suspension was filtered
- customto remove the triethylamine hydrochloride
- washThe filtrate was washed with ˜600 mL of dilute aqueous sodium bicarbonate solution
- customThe organic layer was dried
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-d2f692192ac340f79708f4d4c671764b
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08633227B2
Linked notes
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