Methanesulfonyl chloride → 1-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidine

HRID 449149Notes

Reaction equation

HRID 449149 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:15][S:16](Cl)(=[O:18])=[O:17]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:4]([O:3][C:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][S:16]([CH3:15])(=[O:18])=[O:17])[CH2:10][CH2:9]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

5

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidineYield 100%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-boc-4-hydroxypiperidine (32.2 g, 0.160 mol) in DCM (400 mL) was added TEA (26.8 mL, 0.192 mol), methanesulfonyl chloride (13.6 mL, 0.176 mol), DMAP (0.20 g, 0.0016 mol) at 0° C. under nitrogen atmosphere. The resulting mixture was slowly warmed to rt and stirred at the same temperature overnight. The mixture was washed with sat. aq. NaHCO3 (3×80 mL), brine (2×80 mL), and dried over anhydrous sodium sulfate. The filtrate was concentrated to give crude 4-methanesulfonyloxypiperidine-1-carboxylic acid tert-butyl ester as a white solid, 44.7 g (yield: 100%). 1H-NMR (CDCl3, 400 MHz): δ 1.47 (s, 9H), 1.80-1.85 (m, 2H), 1.95-1.99 (m, 2H), 3.05 (s, 3H), 3.28-3.34 (m, 2H), 3.68-3.74 (m, 2H), 4.89 (m, 1H) ppm. The crude product was used in the next step without further purification.

Workup

  1. washThe mixture was washed with sat. aq. NaHCO3 (3×80 mL), brine (2×80 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-caebbb415b824b2fa716ee6b124f2bc3
Source dataset
uspto-grants-2013_07
Patent number
US08481733B2

Reaction notes

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