Methanol → HCID 22645401, compound

HRID 2414277Notes

Reaction equation

HRID 2414277 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][C:11]([CH3:28])([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2OS(C(F)(F)F)(=O)=O)[CH:10]([CH3:29])[CH2:9]1)(=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].C(N(CC)CC)C.[CH3:37][OH:38].CN(C)[CH:41]=[O:42]>>[C:1]([N:8]1[CH2:13][CH2:12][C:11]([CH3:28])([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:37]([O:42][CH3:41])=[O:38])[CH:15]=2)[CH:10]([CH3:29])[CH2:9]1)(=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]

Participants

5

Reactant 4

HCID 887MethanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 22645412HCID 22645412, compound

Product 1

HCID 22645401HCID 22645401, compound

Conditions

Temperature
60 °C

Procedure

To a solution of 1-hexanoyl-3,4-dimethyl-4-(trifluoromethanesulfonyloxyphenyl)piperidine (Preparation 6, 267 mg, 0.48 mmol) in anhydrous N,N-dimethylformamide (2 mL) was added triethylamine (0.18 mL) and methanol (0.4 mL). The mixture was de-oxygenated by evacuating and flushing with nitrogen five times. Palladium(II) acetate (4.4 mg) and 1,1′-bis(diphenylphosphino)ferrocene (8 mg) were added and the solution was purged with carbon monoxide. The reaction mixture was heated to 60° C. under an atmosphere of carbon monoxide for 7 hours then it was cooled to room temperature and diluted with saturated aqueous sodium chloride solution (10 mL). The phases were separated and the aqueous layer was extracted with dichloromethane (4×15 mL). The combined organics were dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography on silica gel (50 g) eluted with hexane:ethyl acetate:0.880 ammonia (66:33:1). The title compound was obtained as a pale yellow oil (110 mg).

Workup

  1. customby evacuating
  2. customflushing with nitrogen five times
  3. additionPalladium(II) acetate (4.4 mg) and 1,1′-bis(diphenylphosphino)ferrocene (8 mg) were added
  4. customthe solution was purged with carbon monoxide
  5. temperatureit was cooled to room temperature
  6. additiondiluted with saturated aqueous sodium chloride solution (10 mL)
  7. customThe phases were separated
  8. extractionthe aqueous layer was extracted with dichloromethane (4×15 mL)
  9. dry with materialThe combined organics were dried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by column chromatography on silica gel (50 g)
  12. washeluted with hexane

Sources & evidence

ORD record
ord-152bba6282b342558f1c490d1390b67a
Source dataset
uspto-grants-2004_11
Patent number
US06812236B2

Reaction notes

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