Triethylamine → 1-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidine

HRID 389445Notes

Reaction equation

HRID 389445 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.C(N(CC)CC)C.[CH3:22][S:23](Cl)(=[O:25])=[O:24]>C(Cl)Cl.CN(C)C1C=CN=CC=1>[CH3:22][S:23]([O:1][CH:2]1[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]1)(=[O:25])=[O:24]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 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

A solution of tert-butyl 4-hydroxypiperidine-1-carboxylate (32.2 g, 0.160 mol) in DCM (400 mL) cooled to 0° C., was treated with triethylamine (26.8 mL, 0.192 mol), methanesulfonyl chloride (13.6 mL, 0.176 mol), and 4-dimethylaminopyridine (0.20 g, 0.0016 mol) at 0° C. under nitrogen atmosphere. The resulting mixture was slowly warmed to RT and stirred overnight. The mixture was washed with saturated aqueous NaHCO3 (3×80 mL), brine (2×80 mL), and dried over anhydrous sodium sulfate. The filtrate was concentrated to provide 44.7 g (100%) of tert-butyl 4-[(methylsulfonyl)oxy]piperidine-1-carboxylate as a white solid. The product was used to next step without further purification. 1H NMR (400 MHz, CDCl3): δ 4.89 (tt, J=7.77, 3.85 Hz, 1H), 3.67-3.75 (m, 2H), 3.31 (ddd, J=13.71, 8.27, 3.79 Hz, 2H), 3.04 (s, 3H), 1.93-2.02 (m, 2H), 1.77-1.88 (m, 2H), 1.47 (s, 9H).

Workup

  1. washThe mixture was washed with saturated aqueous 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-54f437adb8a94053aa3378a709e09092
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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