Acetone → tert-Butyl 3-(((methylsulfonyl)oxy)methyl)piperidine-1-carboxylate

HRID 896510Notes

Reaction equation

HRID 896510 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([CH2:14][OH:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.CC(C)=O.[CH3:27][S:28](Cl)(=[O:30])=[O:29]>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([CH2:14][O:15][S:28]([CH3:27])(=[O:30])=[O:29])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 180AcetoneHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 2763851tert-Butyl 3-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 22647269tert-Butyl 3-(((methylsulfonyl)oxy)methyl)piperidine-1-carboxylateYield 93.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 3-hydroxymethylpiperidine-1-carboxylic acid tert-butyl ester (15.0 g, 69.7 mmol) and triethylamine (14.6 mL, 104.5 mmol) in dichloromethane (270 mL) was stirred on a bath of ice and acetone. A solution of methanesulfonyl chloride (5.5 mL, 71.1 mmol) in dichloromethane (25 mL) was added dropwise at a rate which kept the internal temperature remained below 0° C. (the addition required about 20 minutes). The mixture was stirred on an ice bath for 2.5 hours, then was concentrated under vacuum. The residue was dissolved in ethyl acetate, and the mixture was filtered to remove a white crystalline solid. The filtrate was concentrated under vacuum to provide an orange gum. Purification by flash chromatography (50% ethyl acetate in hexane) provided a white solid (19.12 g, 93%). 1H NMR (300 MHz, CDCl3) δ4.10 (m, 2H), 3.95 (bd, J=13 Hz, 1H), 3.81 (dt, J=14, 4 Hz, 1H), 3.03 (s, 3H), 2.92 (ddd, J=14, 10, 3 Hz, 1H), 2.79 (dd, J=13, 10 Hz, 1H), 1.97 (m, 1H), 1.83 (m, 1H), 1.68 (m, 1H), 1.49 (m, 1H), 1.46 (s, 9H), 1.30 (m, 1H).

Workup

  1. customremained below 0° C.
  2. additionthe addition required about 20 minutes)
  3. concentrationwas concentrated under vacuum
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. filtrationthe mixture was filtered
  6. customto remove a white crystalline solid
  7. concentrationThe filtrate was concentrated under vacuum
  8. customto provide an orange gum
  9. customPurification by flash chromatography (50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-2722c3f5943748bbba54af000118a8bc
Source dataset
uspto-grants-2005_07
Patent number
US06919356B2

Reaction notes

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