tert-Butanol → 1,1-Dimethylethyl 4-fluoro-4-(4-fluorobenzoyl)-1-piperidinecarboxylate

HRID 1961633Notes

Reaction equation

HRID 1961633 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:22])[C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(O)(C)C.C(O[K])(C)(C)C.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:44])(=O)=O)=CC=1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([F:44])([C:14](=[O:22])[C:15]2[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 588007N-Fluorobenzenesulfonimide3×HCID 7016484tert-butyl 4-(4-fluorobenzoyl)piperidine-1-carboxylateHCID 178418922HCID 178418922, compound3×

Product 1

HCID 179792081,1-Dimethylethyl 4-fluoro-4-(4-fluorobenzoyl)-1-piperidinecarboxylateYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

4-(4-Fluoro-benzoyl)-piperidine-1-carboxylic acid tert-butyl ester in 0.5 mL of DMF was added to a solution at 0° C. containing 0.5 mL of tBuOH, (0.109 mg, 0.651 mmol) tBuOK and 2 mL of DMF. After 20 min stirring at 0° C., N-Fluorobenzenesulfonimide (0.246 g, 0.781 mmol) was added portionwise. The reaction was stirred at 0° C. during 45 min. and (0.55 g, 0.33 mmol) of tBuOK were added at 0° C. and 10 min later (0.123 g, 0.390 mmol) of N-Fluorobenzenesulfonimide. Each 0.5 h two more additions of (0.55 g, 0.33 mmol) tBuOK and (0.123 g, 0.390 mmol) N-Fluorobenzenesulfonimide were repited. 1 h later of the last addition the reaction was quenched with 4 mL of water and the DMF was removed under vacuum. The water was extracted with ethyl acetate and the combined organic phases were purified with column chromatography on silica using n-heptane-EtOAc (3:1). The product fractions were concentrated to give 0.122 g (0.375 mmol, 58% yield) of a yellow oil. MS (m/e): 326.1 (M+H+).

Workup

  1. stirringThe reaction was stirred at 0° C. during 45 min.
  2. addition1 h later of the last addition the reaction
  3. customwas quenched with 4 mL of water
  4. customthe DMF was removed under vacuum
  5. extractionThe water was extracted with ethyl acetate
  6. customthe combined organic phases were purified with column chromatography on silica
  7. concentrationThe product fractions were concentrated

Sources & evidence

ORD record
ord-bef2989722e743189c6bc411716684fc
Source dataset
uspto-grants-2013_04
Patent number
US08415350B2

Reaction notes

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