Triethylamine → Tert-butyl (3R)-3-(methanesulfonyloxy)pyrrolidine-1-carboxylate

HRID 2283449Notes

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, 1 H), 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-58c923d486e142f8bc268f4b930ad359
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09145396B2

Reaction notes

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