1-Phenethylamine, (+)- → HCID 15604588, compound

HRID 418778Notes

Reaction equation

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

Participants

Conditions

Temperature: 50 °C

Procedure

To a stirred solution of racemic 2-{2-[5-fluoro-2-(methyloxy)phenyl]-2-methylpropyl}-2-(trifluoromethyl)oxirane (600 mg, 2.05 mmol), which may be prepared according to WO04/063163, in anhydrous EtOH (3 mL) was added (R)-(+)-1-phenylethylamine (1.31 mL, 10.3 mmol). The reaction mixture was then stirred and heated at 50° C. under nitrogen for 5 days, cooled to room temperature and evaporated in vacuo. The residue was applied to a 70 g silica SPE cartridge and eluted with 0.5% NH3 in toluene. The appropriate fractions were combined and evaporated in vacuo to give a colourless oil (991 mg). 710 mg of this oil was separated by chiral HPC on a 2 inch×15 cm Chiralpak AD column eluted with 25% acetonitrile/ammonium phosphate (pH 4.9) with a flow rate of 70 mL/min to give Intermediate 19 (2S isomer, 230 mg) after 17.5 min and Intermediate 20 (2R isomer, 200 mg) after 24.8 min.

Workup

temperaturecooled to room temperature
customevaporated in vacuo
washeluted with 0.5% NH3 in toluene
customevaporated in vacuo

Sources & evidence

ORD record: ord-ef0171233594455285cc6a80cbab8663
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093281B2

Reaction notes

Loading…