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

HRID 132747Notes

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 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, and 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-9c8995769f3b48628af14cceaf5c4525
Source dataset: uspto-grants-2008_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07388004B2

Reaction notes

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