Hydrochloric Acid → (+)-4-[(4-Fluorophenoxy)phenyl]methyl-piperidine

HRID 1058779

Reaction equation

[C:1]1([CH:7]([CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].C([O-])(=[O:24])C1C=CC=CC=1.[K+].[F:27][C:28]1[CH:33]=[CH:32][C:31](F)=[CH:30][CH:29]=1.[Na+].[Cl-].Cl>CS(C)=O.CO.O>[F:27][C:28]1[CH:33]=[CH:32][C:31]([O:24][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=2[CH2:7][CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:30][CH:29]=1

Participants

Conditions

Temperature: 72.5 °C

Procedure

The alcohol prepared above (2.7 g, 9.3 mmol) dissolved in DMSO (25 mL) was added over an NaH (60%, 0.6 g) suspension in DMSO (5 mL). Potassium benzoate (1.53 g, 9.63 mmol) and 1,4-difluorobenzene (1.3 mL, 11.9 mmol) were added and the mixture was heated (70-75° C.) until the starting substance disappeared. The reaction mixture was poured into water and saturated aqueous NaCl solution, and extracted with ether. The oil obtained was refluxed with a mixture of methanol (40 mL) and an aqueous hydrochloric acid (40 mL) solution for 1 h. Isolation of the product using the customary methodology provided (+)-4-[(4-fluorophenoxy)phenyl]methyl-piperidine as an oil in a 54% yield. Treatment of 0.5 g (1.75 mmol) of this oil with D-dibenzoyltartaric acid in ethanol (96%, 30 mL) provided a precipitate which was filtered (m.p.=198-199° C.). The aminoether was released yielding a white solid with a 96% ee, m.p.=102-104° C., and [α]546+15, c=0.105, CHCl3).

Workup

extractionextracted with ether
customThe oil obtained

Sources & evidence

ORD record: ord-49fa5571b1d440ebad6f0f55ec530ec2
Source dataset: uspto-grants-2003_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06518284B2

Linked notes

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