Dimethyl Sulfate → Benzyl 4-(3-fluoro-4-methoxyphenyl)-3-hydroxypiperidine-1-carboxylate

HRID 1176642Notes

Reaction equation

HRID 1176642 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:16])[CH2:11][CH:10]2[OH:25])[CH:5]=[CH:6][C:7]=1[OH:8].[C:26](=O)([O-])[O-].[K+].[K+].S(OC)(OC)(=O)=O>CC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:16])[CH2:11][CH:10]2[OH:25])[CH:5]=[CH:6][C:7]=1[O:8][CH3:26]

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 11430Potassium CarbonateHCID 68503284HCID 68503284, compound

Product 1

HCID 68500832Benzyl 4-(3-fluoro-4-methoxyphenyl)-3-hydroxypiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A solution of 0.069 g of benzyl 4-(3-fluoro-4-hydroxyphenyl)-3-hydroxypiperidine-1-carboxylate in 5 ml of acetone is admixed with 0.034 g of potassium carbonate and 0.019 ml of dimethyl sulphate. The reaction mixture is stirred at reflux over 5 hours, cooled and filtered through Hyflo. The filtercake is washed with 2×5 ml of acetone and the filtrate is concentrated by evaporation. The residue is taken up in 30 ml of tert-butyl methyl ether, washed with 10 ml of brine, dried over sodium sulphate and concentrated by evaporation. The title compound is obtained as a colourless oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.38 (2:1 EtOAc-heptane); Rt=4.32.

Workup

  1. temperatureat reflux over 5 hours
  2. temperaturecooled
  3. filtrationfiltered through Hyflo
  4. washThe filtercake is washed with 2×5 ml of acetone
  5. concentrationthe filtrate is concentrated by evaporation
  6. washwashed with 10 ml of brine
  7. dry with materialdried over sodium sulphate
  8. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-e8921f16be8f454382eeddec131f14e1
Source dataset
uspto-grants-2010_11
Patent number
US07842688B2

Reaction notes

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