3-Chloro-1-propanol → 4-(p-Fluorobenzoyl)-1-(3-hydroxypropyl)piperidine

HRID 2397442Notes

Reaction equation

HRID 2397442 reaction equation
Cl.[F:2][C:3]1[CH:16]=[CH:15][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[O:8])=[CH:5][CH:4]=1.Cl[CH2:18][CH2:19][CH2:20][OH:21].C(=O)(O)[O-].[Na+]>C(O)CCC>[F:2][C:3]1[CH:4]=[CH:5][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([CH2:18][CH2:19][CH2:20][OH:21])[CH2:11][CH2:10]2)=[O:8])=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 123133-Chloro-1-propanol2×HCID 516892Sodium BicarbonateHCID 3084438p-Fluorophenyl 4-piperidyl ketone hydrochloride

Product 1

HCID 124044224-(p-Fluorobenzoyl)-1-(3-hydroxypropyl)piperidine

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A mixture of 24.3 g. (0.1 mole) of 4-(p-fluorobenzoyl)-piperidine hydrochloride, 12.5 g. (0.125 mole) of 3-chloropropanol and 42.0 g. (0.5 mole) of sodium bicarbonate in 500 ml. of n-butanol was stirred at reflux for 15 hours. An additional 3.0 g. (0.025 mole) of 3-chloropropanol was added after thin layer chromatography showed incomplete reaction and the reaction was continued for 3 hours. The cooled reaction mixture was filtered, the filtrate concentrated at reduced pressure and the residual oil crystallized by trituration in isopropyl ether. The tan solid weighed 23 g. (87%) and melted at 107°-109° C. Recrystallization from benzene-isooctane gave 17.7 g. of material melting at 111°-112° C.

Workup

  1. additionA mixture of 24.3 g
  2. temperatureat reflux for 15 hours
  3. customreaction
  4. customThe cooled reaction mixture
  5. filtrationwas filtered
  6. concentrationthe filtrate concentrated at reduced pressure
  7. customthe residual oil crystallized by trituration in isopropyl ether
  8. customRecrystallization from benzene-isooctane
  9. customgave 17.7 g

Sources & evidence

ORD record
ord-a44b056fd690406bb86c6e405a299395
Source dataset
uspto-grants-1977_05
Patent number
US04021552

Reaction notes

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