Ethanol → 1-Acetyl-piperidine-4-carboxylic acid [2-(4-fluoro-phenyl)-1-hydroxymethyl-2-oxo-ethyl]-amide

HRID 2288963Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:22])[CH2:9][NH:10][C:11]([CH:13]2[CH2:18][CH2:17][N:16]([C:19](=[O:21])[CH3:20])[CH2:15][CH2:14]2)=[O:12])=[CH:4][CH:3]=1.C[CH2:24][OH:25].C(=O)(O)[O-].[Na+].C=O>O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8](=[O:22])[CH:9]([NH:10][C:11]([CH:13]2[CH2:14][CH2:15][N:16]([C:19](=[O:21])[CH3:20])[CH2:17][CH2:18]2)=[O:12])[CH2:24][OH:25])=[CH:6][CH:7]=1

Participants

Conditions

Temperature: -5 °C

Procedure

To a 250 mL 3-neck flask under n2 is added 8.00 g (26.1 mmol) of 1-Acetyl-piperidine-4-carboxylic acid [2-(4-fluoro-phenyl)-2-oxo-ethyl]amide, prepared as in Part A, to a 3:1 solution of EtOH:H2O (40 mL). While stirring the resultant solution at room temperature, 500 mg (5.95 mmol) of sodium bicarbonate is added followed by subsequent addition of 4.24 mL (52.23 mmol) of 37% formaldehyde over 5 min. The mixture is stirred for 1.5 h and then 20 mL of H2O is added. The reaction is cooled to -5° C. at which point a precipitate formed and is filtered. The mother liquor is again cooled to give a second crop of product and the combined lots are dried in-vacuo overnight at 65° C. to yield 1-Acetyl-piperidine-4-carboxylic acid [2-(4-fluoro-phenyl)-1-hydroxymethyl-2-oxo-ethyl]-amide as a white solid.

Workup

additionTo a 250 mL 3-neck flask under n2 is added
customformed
filtrationis filtered
temperatureThe mother liquor is again cooled
customto give a second crop of product
customthe combined lots are dried in-vacuo overnight at 65° C.

Sources & evidence

ORD record: ord-6b281569e4b245259637f8b0a38ca6b6
Source dataset: uspto-grants-2000_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06090825

Reaction notes

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