Ethyl Acetate → tert-Butyl 3-fluoro-4-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate

HRID 1427001Notes

Reaction equation

HRID 1427001 reaction equation
O[CH:2]1[CH:7]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([O:16][CH3:17])=[O:15])=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:3]1.COCCN(S(F)(F)[F:35])CCOC.C(=O)(O)[O-].[Na+].C(OCC)(=O)C>ClCCl>[F:35][CH:2]1[CH:7]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([O:16][CH3:17])=[O:15])=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:3]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 2734690(Bis(2-methoxyethyl)amino)sulfur trifluorideHCID 53949513Tert-butyl 3-hydroxy-4-(4-methoxycarbonylphenyl)piperidine-1-carboxylate

Product 1

HCID 86730315tert-Butyl 3-fluoro-4-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylateYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 3-hydroxy-4-(4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate described in Production Example 6-2 (518 mg, 1.54 mmol) was dissolved in dichloromethane (15 mL), [bis-(2-methoxyethyl)amino]sulfur trifluoride (0.313 mL, 1.70 mmol) was added at −78° C. over 3 minutes, and the mixture was stirred for 1 hour while warming to room temperature. A saturated aqueous sodium bicarbonate solution and ethyl acetate were serially added to the reaction mixture. The aqueous layer was extracted with ethyl acetate three times and then the organic layers were combined, dried over anhydrous sodium sulfate, and filtered. The solvent was evaporated and the resultant residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=19:1-3:2) to obtain the title compound (402 mg, 77%).

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate three times
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. customThe solvent was evaporated
  5. customthe resultant residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=19:1-3:2)

Sources & evidence

ORD record
ord-bad5f5bbdf834c92bd257586f5f88ceb
Source dataset
uspto-grants-2015_01
Patent number
US08933099B2

Reaction notes

Loading…