4-Toluenesulfonyl chloride → tert-Butyl (2S)-2-(((4-methylbenzene-1-sulfonyl)oxy)methyl)pyrrolidine-1-carboxylate

HRID 1909652Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][OH:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:15]1([CH3:25])[CH:20]=[CH:19][C:18]([S:21](Cl)(=[O:23])=[O:22])=[CH:17][CH:16]=1>N1C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][O:14][S:21]([C:18]1[CH:19]=[CH:20][C:15]([CH3:25])=[CH:16][CH:17]=1)(=[O:23])=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 0 °C

Procedure

(S)-2-Hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (10 g, 0.05 mol) was taken into anhydrous pyridine (51 mL). The reaction was cooled to 0° C. and p-toluenesulfonyl chloride (10.42 g, 0.055 mol) in anhydrous pyridine (25 mL) was added dropwise over 10 min. The reaction ran at 0° C. for 2 h. and then allowed to warm to room temperature overnight. The mixture was concentrated to dryness and the residue was taken into ethyl acetate (200 mL) and washed with 0.5N HCl (50 mL). The ethyl acetate was then washed with aqueous sodium bicarbonate (100 mL), brine, dried over sodium sulfate and concentrated to dryness to obtain the title product (17.55 g, 0.049 mol, 99% yield); MS; m/z 355, found 356 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 1.28 (s, 9H), 1.72 (s, 3H), 1.90 (s, 1H), 2.42 (s, 3H), 3.14-3.23 (m, 2H), 3.84 (s, 1H), 3.97-4.06 (m, 2H), 7.49 (d, J=8.0, 2H), 7.78 (d, J=8.0, 2H).

Workup

temperatureto warm to room temperature overnight
concentrationThe mixture was concentrated to dryness
washwashed with 0.5N HCl (50 mL)
washThe ethyl acetate was then washed with aqueous sodium bicarbonate (100 mL), brine
dry with materialdried over sodium sulfate
concentrationconcentrated to dryness

Sources & evidence

ORD record: ord-caa34b5a6ca243b6ae68594f3481b2e1
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598359B2

Reaction notes

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