Benzyl(methoxymethyl)((trimethylsilyl)methyl)amine → 1-[(3RS,4SR)-1-Benzyl-4-(2,4-difluoro-phenyl)-pyrrolidin-3-yl]-ethanone

HRID 559284Notes

Reaction equation

CO[CH2:3][N:4]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:5][Si](C)(C)C.[F:17][C:18]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=1/[CH:25]=[CH:26]/[C:27](=[O:29])[CH3:28]>C(Cl)Cl.FC(F)(F)C(O)=O>[CH2:10]([N:4]1[CH2:3][CH:25]([C:19]2[CH:20]=[CH:21][C:22]([F:24])=[CH:23][C:18]=2[F:17])[CH:26]([C:27](=[O:29])[CH3:28])[CH2:5]1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

Conditions

Temperature: 25 °C

Procedure

A solution of N-(methoxymethyl)-N-(phenylmethyl)-N-(trimethylsilyl)methylamine (7.82 g, 32.9 mmol) in CH2Cl2 (40 mL) was added dropwise, over a 30 minutes period, to a stirred solution of (E)-4-(2,4-difluoro-phenyl)-but-3-en-2-one (4.0 g, 21.9 mmol) and trifluoroacetic acid (0.17 mL, 0.21 mmol) in CH2Cl2 (10 mL) at 0° C. The ice bath was removed, and the solution was stirred at 25° C. for an additional 48 h. It was then concentrated and purification by flash chromatography (SiO2, CH2Cl2/MeOH 98:2) afforded 6.2 g (89%) of the title compound as a yellow oil. ES-MS m/e: 316.1 (M+H+).

Workup

customThe ice bath was removed
concentrationIt was then concentrated
custompurification by flash chromatography (SiO2, CH2Cl2/MeOH 98:2)

Sources & evidence

ORD record: ord-e46eea457e0e496eade5ae5c0a9c283f
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08063075B2

Reaction notes

Loading…