Hydrochloric Acid → 3-(4-Azetidin-3-yl-phenyl)-5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazole hydrochloride salt

HRID 1961550Notes

Reaction equation

C(OC([N:8]1[CH2:11][CH:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH2:22][C:21]([C:27]4[CH:32]=[C:31]([Cl:33])[CH:30]=[C:29]([Cl:34])[CH:28]=4)([C:23]([F:26])([F:25])[F:24])[O:20][N:19]=3)=[CH:14][CH:13]=2)[CH2:9]1)=O)(C)(C)C.Cl>CO>[ClH:33].[NH:8]1[CH2:11][CH:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH2:22][C:21]([C:27]4[CH:28]=[C:29]([Cl:34])[CH:30]=[C:31]([Cl:33])[CH:32]=4)([C:23]([F:24])([F:25])[F:26])[O:20][N:19]=3)=[CH:14][CH:13]=2)[CH2:9]1

Participants

Conditions

Temperature: 70 °C

Procedure

To a stirred solution of 3-{4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}azetidine-1-carboxylic acid tert-butyl ester (Preparation 40, 1 g, 1.94 mmol, 1 eq) in MeOH (10 mL) was purged HCl (g) at 0° C. for 0.5 hours and then reaction mixture was refluxed at 70° C. for 0.5 hours. Progress of reaction was monitored by TLC, after complete consumption of starting material reaction mixture was evaporated under reduced pressure to dryness to give 1.15 g (crude) Which was washed with methyl t-butyl ether (10 mL×2) to afforded 1.1 g (95.21%). 1H-NMR and LC-MS were consistent. 1H NMR (400 MHz, DMSO-d6) δ 4.05 (t, J=8 Hz, 2H), 4.15-4.21 (m, 1H), 4.24-4.39 (m, 4H), 7.55 (d, J=8 Hz, 2H), 7.62 (d, J=1 Hz, 2H), 7.74 (d, J=8 Hz, 2H), 7.81 (t, J=2 Hz, 1H), 8.99 (bs, 2H). LC-MS (m/z):=415 (M+H).

Workup

customreaction mixture
customProgress of reaction
customafter complete consumption of starting material reaction mixture
customwas evaporated under reduced pressure to dryness
customto give 1.15 g (crude) Which
washwas washed with methyl t-butyl ether (10 mL×2)
customto afforded 1.1 g (95.21%)

Sources & evidence

ORD record: ord-7f684ff5aced46b8957a7dda6d59dcc0
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415310B2

Reaction notes

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