Acetic Acid → Despropionyl N-benzyl p-fluoro norfentanyl

HRID 1984982Notes

Reaction equation

[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[CH2:9]([N:16]1[CH2:21][CH2:20][CH2:19][CH2:18][C:17]1=O)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(O)(=O)C.[BH4-].[Na+]>ClCCCl>[CH2:9]([N:16]1[CH2:21][CH2:20][CH:19]([NH:6][C:5]2[CH:7]=[CH:8][C:2]([F:1])=[CH:3][CH:4]=2)[CH2:18][CH2:17]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

Conditions

Temperature: 15 °C

Procedure

A solution of 4-fluoroaniline (32.7 g), N-benzylpiperidinone (106.0 g) and acetic acid (106.0 g) in 1,2-dichlorethane (1200 ml) is brought to a temperature below 15° C. To the stirred solution is added slowly a suspension of acetic acid (495.0 g) and sodium borohydride (31.2 g). After 2 h stirring at 15° C. and another 2 h at r.t., the solvent is removed in vacuo. Ethyl acetate (500 ml) and water (700 ml) are added under stirring and the resulting mixture is neutralised with sodium carbonate (ca. 250 g). The organic phase is separated, washed with a 2 M NaHCO3 solution (100 ml) and water (100 ml) and dried with sodium sulphate. 53.8 g product is obtained as orange crystals after removal of the solvent and recrystallisation from ether/petroleum ether. Mp. 90-92° C.

Workup

customis brought to a temperature below 15° C
additionTo the stirred solution is added slowly
customthe solvent is removed in vacuo
additionEthyl acetate (500 ml) and water (700 ml) are added
stirringunder stirring
customThe organic phase is separated
washwashed with a 2 M NaHCO3 solution (100 ml) and water (100 ml)
dry with materialdried with sodium sulphate

Sources & evidence

ORD record: ord-e8bf3156c3354b13bf9f8886dffbe91c
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07544806B2

Reaction notes

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