Phenol → 5-Hydroxy-5-phenylaminomethyl-2-(4-trifluoromethoxy-phenyl)-hexahydro-cyclopenta[c]pyrrol-1-one

HRID 1887501Notes

Reaction equation

[F:1][C:2]([F:22])([F:21])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:14][CH:13]3[CH2:15][C:16]4([CH2:19][CH:12]3[C:11]2=[O:20])[CH2:18][O:17]4)=[CH:6][CH:5]=1.[NH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C1(O)C=CC=CC=1>O>[OH:17][C:16]1([CH2:18][NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:19][CH:12]2[C:11](=[O:20])[N:10]([C:7]3[CH:6]=[CH:5][C:4]([O:3][C:2]([F:22])([F:21])[F:1])=[CH:9][CH:8]=3)[CH2:14][CH:13]2[CH2:15]1

Participants

Conditions

Temperature: 60 °C

Procedure

rac-(3aR,5S,6aS)-2-[4-(trifluoromethoxy)phenyl]hexahydro-1H-spiro[cyclopenta[c]pyrrole-5,2′-oxiran]-1-one (80 mg, 0.25 mmol), aniline (5 mL) and PhOH (23 mg, 0.24 mmol) were mixed together, and the mixture was stirred for 24 h at 60° C. The solution was then poured into water (25 mL) and extracted with ether (3×20 mL). The combined ether was washed with sodium hydroxide (10%, 3×10 mL), with water (30 mL) and dried over Na2SO4. The solvent was removed and the residue was purified by prep-TLC (petroleum ether:ethyl acetate=1:1) to yield the title compound (25 mg, 24%). 1H NMR (300 MHz, CDCl3): δ 7.57-7.55 (m, 2H), 7.27-7.13 (m, 4H), 7.00-6.93 (m, 3H), 5.26 (bs, 1H), 4.07 (t, 1H, J=9.3 Hz), 3.75-3.73 (m, 1H), 3.34-2.22 (m, 3H), 3.05-2.90 (m, 1H), 2.46-2.42 (m, 1H), 2.02-1.90 (m, 3H); LC-MS: 407.1 [M+1]+.

Workup

extractionextracted with ether (3×20 mL)
washThe combined ether was washed with sodium hydroxide (10%, 3×10 mL), with water (30 mL)
dry with materialdried over Na2SO4
customThe solvent was removed
customthe residue was purified by prep-TLC (petroleum ether:ethyl acetate=1:1)

Sources & evidence

ORD record: ord-1fe27764d4584db994dc023d1aa70b93
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08501768B2

Reaction notes

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