Fluorobenzene → 4-(4-Fluorobenzyl)-1-(2-(4-fluorophenoxy)ethyl)piperidine hydrochloride

HRID 1955185Notes

Reaction equation

HRID 1955185 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([C:10](=O)[C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[CH2:6][CH2:5]1)(=O)[CH3:2].C(N1CCC(C([Cl:28])=O)CC1)(=[O:21])C.[Cl-].[Cl-].[Cl-].[Al+3].[F:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>>[ClH:28].[F:17][C:14]1[CH:15]=[CH:16][C:11]([CH2:10][CH:7]2[CH2:8][CH2:9][N:4]([CH2:1][CH2:2][O:21][C:39]3[CH:40]=[CH:41][C:36]([F:35])=[CH:37][CH:38]=3)[CH2:5][CH2:6]2)=[CH:12][CH:13]=1

Participants

5

Reactant 4

HCID 10008FluorobenzeneHCID 1009501-Acetylpiperidine-4-carbonyl chlorideHCID 1172571-Acetyl-4-(4-fluorobenzoyl)piperidineHCID 6451240Aluminum(III) Chloride

Product 1

HCID 232944164-(4-Fluorobenzyl)-1-(2-(4-fluorophenoxy)ethyl)piperidine hydrochlorideYield 50%

Procedure

1-Acetyl-4-(4-fluorobenzoyl)piperidine. N-acetylisonipecotoyl chloride (2.00 g, 10.5 mmol) was slowly added to a stirred mixture of aluminum trichloride (2.80 g, 21.1 mmol) in fluorobenzene (10 mL). After addition was complete, the mixture was refluxed for 1 h. The mixture was poured into ice and the resulting layers were separated. The aqueous layer was extracted with CH2Cl2 (2×30 mL), the combined organic phase was dried and was concentrated under reduced pressure to afford the title compound as a pale yellow oil (1.30 g, 50%): 1H NMR (CDCl3) 1.50-1.70 (m, 1H), 1.70-2.00 (m, 3H), 2.10 (s, 3H), 2.81 (t, J=12.0 Hz, 1H), 3.15-3.30 (m, 1H), 3.40-3.55 (m, 1H), 3.90 (d, J=13.2 Hz, 1H), 4.57 (d, J=13.2 Hz, 1H), 7.14 (t, J=8.4 Hz, 2H), 7.97 (dd, J=5.7 and 8.4 Hz, 2H).

Workup

  1. additionAfter addition
  2. temperaturethe mixture was refluxed for 1 h
  3. additionThe mixture was poured into ice
  4. customthe resulting layers were separated
  5. extractionThe aqueous layer was extracted with CH2Cl2 (2×30 mL)
  6. customthe combined organic phase was dried
  7. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-1806d76c399e4a1baeaa143029ffa69b
Source dataset
uspto-grants-2000_09
Patent number
US06124323

Reaction notes

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