Acetyl chloride → 1-{3-[1-(3-Fluorophenyl)methylidene]piperidin-1-yl}ethanone

HRID 928078Notes

Reaction equation

HRID 928078 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].Cl.[F:6][C:7]1[CH:8]=[C:9]([CH:13]=[C:14]2[CH2:19][CH2:18][CH2:17][NH:16][CH2:15]2)[CH:10]=[CH:11][CH:12]=1.C(N(C(C)C)CC)(C)C>C1COCC1.O>[F:6][C:7]1[CH:8]=[C:9]([CH:13]=[C:14]2[CH2:19][CH2:18][CH2:17][N:16]([C:1](=[O:3])[CH3:2])[CH2:15]2)[CH:10]=[CH:11][CH:12]=1

Participants

6

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 709838913-[1-(3-Fluorophenyl)methylidene]piperidine hydrochloride2×

Product 1

HCID 709845881-{3-[1-(3-Fluorophenyl)methylidene]piperidin-1-yl}ethanone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Acetyl chloride (0.515 mL) was added to a mixture of 3-[1-(3-fluorophenyl)methylidene]-piperidine hydrochloride (Intermediate 226, 1.5 g) and N,N-di-isopropyl-N-ethylamine (2.52 mL) in anhydrous THF (50 mL) at 0° C. under nitrogen. The mixture was allowed to warm to room temperature and was stirred for 2 hours. The mixture was diluted with water (100 mL) and extracted with ether, washed with brine, dried (Na2SO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 75-100% to give 1-{3-[1-(3-fluorophenyl)-methylidene]piperidin-1-yl}ethanone (1.38 g).

Workup

  1. extractionextracted with ether
  2. washwashed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customThe filtrate was evaporated to dryness
  6. customthe residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 75-100%

Sources & evidence

ORD record
ord-4354b4a830df48c2854eeaec51d107b0
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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