Triethylamine → 4-Fluoro-4-(methylsulfonyloxymethyl)-1-piperidinecarboxylic acid tert-butyl ester

HRID 2035615Notes

Reaction equation

HRID 2035615 reaction equation
[F:1][C:2]1([CH2:15][OH:16])[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.C(N(CC)CC)C.[CH3:24][S:25](Cl)(=[O:27])=[O:26].C([O-])(O)=O.[Na+]>ClCCl>[F:1][C:2]1([CH2:15][O:16][S:25]([CH3:24])(=[O:27])=[O:26])[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9])[CH2:6][CH2:7]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 22248400tert-Butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 222484024-Fluoro-4-(methylsulfonyloxymethyl)-1-piperidinecarboxylic acid tert-butyl esterYield 92.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 0° C. solution of tert-butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate (2.60 g, 11.1 mmol) and triethylamine (2.33 mL, 16.7 mmol) in 55 mL dichloromethane was added neat methanesulfonyl chloride (0.949 mL, 12.3 mmol) dropwise by syringe. The reaction mixture was slowly warmed to ambient temperature and stirred at ambient temperature for 17 hours. Saturated NaHCO3 was added, the mixture was extracted with dichloromethane, and combined extracts were dried (Na2SO4), filtered, and concentrated. The crude was purified on silica gel (4:1 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate) to give the title compound (3.2 g, 92.2% yield) as a white powder.

Workup

  1. extractionthe mixture was extracted with dichloromethane
  2. dry with materialwere dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude was purified on silica gel (4:1 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-16f672bfd7424303a5b6d42c500277c1
Source dataset
uspto-grants-2013_11
Patent number
US08575145B2

Reaction notes

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