Triethylamine → (S)-1-Benzyl-3-mesyloxypyrrolidine

HRID 1765109Notes

Reaction equation

[CH2:1]([N:8]1[CH2:12][CH2:11][C@H:10]([OH:13])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:21][S:22](Cl)(=[O:24])=[O:23].C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[CH2:1]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][S:22]([CH3:21])(=[O:24])=[O:23])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

(S)-1-Benzyl-3-hydroxypyrrolidine (20.2 g, 114 mmol) was dissolved in toluene (200 mL). To this stirred solution, triethylamine (20 mL, 142 mmol) was added followed by methanesulfonyl chloride (10.5 mL, 136 mmol) during a period of 40 min at 0° C. The resultant slurry was allowed to stir for two hours at 0° C. and 7% sodium bicarbonate (200 mL) was added to the reaction mixture. Organic layer was separated, and the aqueous layer was extracted with toluene (3×100 mL). The combined organic layers were washed with saturated sodium bicarbonate (3×200 mL), dried over Na2SO4 and concentrated under reduced pressure to give (S)-methanesulfonic acid 1-benzyl-pyrrolidin-3-yl ester as a yellow oil (28 g, 96%). The material was used directly for next step without purification. 1H NMR (400 MHz, CDCl3) δ 7.34-7.17 (m, 5H), 5.24-5.18 (m, 1H), 3.71 (d, JAB=13.0 Hz, 1H), 3.64 (d, JAB=13.0 Hz, 1H), 3.01 (s, 3H), 2.89-2.80 (m, 3H), 2.56-2.50 (m, 1H), 2.38-2.31 (m, 1H), 2.14-2.07 (m, 1H).

Workup

customOrganic layer was separated
extractionthe aqueous layer was extracted with toluene (3×100 mL)
washThe combined organic layers were washed with saturated sodium bicarbonate (3×200 mL)
dry with materialdried over Na2SO4
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-cd74b3ce4bf34e53a5d7c5ec59545073
Source dataset: uspto-grants-2007_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07226931B2

Reaction notes

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