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

HRID 549517Notes

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 (which may be prepared according to WO04/063163, 600 mg, 2.05 mmol) 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 overnight and then 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 (991.4 mg). 710 mg of this oil was separated by chiral HPC on a 2 inch×15 cm Chiralpak AD column eluted with 25% acetonitrile/0.25M ammonium phosphate (pH 4.9) with a flow rate of 70 mL/min to give Intermediate 9 (2S isomer, 230 mg) after 17.5 min and Intermediate 10 (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-435c9cc5efe942beb227892f0c719179
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07943651B2

Reaction notes

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