Ammonia → 1-(4-Aminomethylphenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-methoxyphenyl)azetidin-2-one

HRID 133710Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:32])[CH2:9][CH2:10][CH:11]2[C:14](=[O:15])[N:13]([C:16]3[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=3)[CH:12]2[C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.N.[H][H]>C(O)C.[Ni]>[NH2:21][CH2:20][C:19]1[CH:22]=[CH:23][C:16]([N:13]2[CH:12]([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=3)[CH:11]([CH2:10][CH2:9][CH:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[OH:32])[C:14]2=[O:15])=[CH:17][CH:18]=1

Participants

Conditions

Temperature: 60 °C

Procedure

1.22 g of 4-[3-[3-(4-fluorophenyl)-3-hydroxypropyl]-2-(4-methoxyphenyl)-4-oxoazetidin-1-yl]-benzonitrile (4) were dissolved in 90 ml of ethanol. 10 ml of conc. ammonia solution and an excess of Raney nickel were added, and the mixture was stirred at 60° C. and a hydrogen pressure of 10 bar for 8 h. Overnight, the reaction mixture cooled to room temperature. The next day, the catalyst was removed, the filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromatography using dichloromethane/methanol/ammonia solution 10/1/0.1. This produced 1-(4-aminomethylphenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-methoxyphenyl)-azetidin-2-one (5) of molecular weight 434.51 (C26H27FN2O3); MS (ESI): 418.2 (MH+-NH3).

Workup

temperatureOvernight, the reaction mixture cooled to room temperature
customThe next day, the catalyst was removed
concentrationthe filtrate was concentrated under reduced pressure
customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record: ord-0d529adef83b4edd875390a343a493e9
Source dataset: uspto-grants-2008_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07390790B2

Reaction notes

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