Dimethyl Sulfate → Tert-butyl 3-hydroxy-4-(4-methoxyphenyl)piperidine-1-carboxylate

HRID 1176276Notes

Reaction equation

HRID 1176276 reaction equation
[OH:1][CH:2]1[CH:7]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:3]1.[C:22](=O)([O-])[O-].[K+].[K+].S(OC)(OC)(=O)=O>CC(C)=O>[OH:1][CH:2]1[CH:7]([C:8]2[CH:9]=[CH:10][C:11]([O:14][CH3:22])=[CH:12][CH:13]=2)[CH2:6][CH2:5][N:4]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:3]1

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 11430Potassium CarbonateHCID 21713087(3S,4S)-tert-Butyl 3-hydroxy-4-(4-hydroxyphenyl)piperidine-1-carboxylate

Product 1

HCID 45074240Tert-butyl 3-hydroxy-4-(4-methoxyphenyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A suspension of 15.07 g of tert-butyl 3-hydroxy-4-(4-hydroxyphenyl)piperidine-1-carboxylate and 10.10 g of potassium carbonate in 260 ml of acetone is admixed with 5.43 ml of dimethyl sulphate and stirred at reflux over 7 hours. The reaction mixture is cooled to room temperature and concentrated by evaporation. The residue is partitioned between diethyl ether and a 1:1 25% conc. ammonia-water mixture. The organic phase is washed with water, 2N NaOH (2×) and brine, dried over sodium sulphate and concentrated by evaporation. The crude title compound is obtained as a white solid from the residue. Rf=0.30 (1:1 EtOAc-heptane); Rt=4.22.

Workup

  1. temperatureat reflux over 7 hours
  2. concentrationconcentrated by evaporation
  3. customThe residue is partitioned between diethyl ether
  4. washThe organic phase is washed with water, 2N NaOH (2×) and brine
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-26d3a8fc3dce42c9aa846a4904b4199f
Source dataset
uspto-grants-2010_11
Patent number
US07842688B2

Reaction notes

Loading…