4-Toluenesulfonyl chloride → (1-Acetylpiperidin-4-yl)methyl 4-methylbenzenesulfonate

HRID 2277050Notes

Reaction equation

[CH3:1]CN(CC)CC.[OH:8][CH2:9][CH:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18]C)=O)[CH2:12][CH2:11]1.[S:20](Cl)([C:23]1[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=1)(=[O:22])=[O:21]>CN(C1C=CN=CC=1)C.C(Cl)Cl.CCOC(C)=O>[CH3:27][C:26]1[CH:28]=[CH:29][C:23]([S:20]([O:8][CH2:9][CH:10]2[CH2:11][CH2:12][N:13]([C:16](=[O:18])[CH3:1])[CH2:14][CH2:15]2)(=[O:22])=[O:21])=[CH:24][CH:25]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Et3N (0.16 g, 1.60 mmol) and DMAP (0.39 g, 0.32 mmol) were added to a solution of methyl 4-(hydroxymethyl)piperidine-1-carboxylate (1.0 g, 3.20 mmol) in DCM (20 mL). The reaction mixture was cooled to 0° C. and TsCl (0.73 g, 3.80 mmol) was added. The reaction mixture was stirred for 1 h at room temperature, diluted with EtOAc, washed with water, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by flash chromatography (50% EtOAc:hexane) gave (1-acetylpiperidin-4-yl)methyl 4-methylbenzenesulfonate as a pale yellow semi-solid. Yield (1.2 g, 63%); 1H NMR (400 MHz, CDCl3); δ 7.77 (d, J=8.4 Hz, 2H), 7.63 (d, J=7.6 Hz, 2H), 4.64 (d, J=14.4 Hz, 2H), 3.92 (dd, J=6.0, 2.4 Hz, 2H), 3.84 (t, J=3.2 Hz, 4H), 3.02 (d, J=13.6 Hz, 2H), 2.54-2.49 (m, 2H), 2.45 (s, 3H), 1.72-1.62 (m, 1H), 1.16 (dt, J=12.4, 3.6 Hz, 1H); MS: m/z 312.05 [M+H]+.

Workup

washwashed with water
dry with materialdried over anhydrous Na2SO4
concentrationconcentrated under reduced pressure
customPurification by flash chromatography (50% EtOAc:hexane)

Sources & evidence

ORD record: ord-a2688d4bbe8d4b9c90a53f65005e3ba2
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133154B2

Reaction notes

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