Citric Acid → 6-fluoro-4-hydroxy-4-phenyl-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one

HRID 19678

Reaction equation

[C:1]([C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[NH:16][C:17](N1C=CN=C1)=[O:18])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:24][C:25]([F:29])([F:28])[CH2:26][NH2:27].C(O)(=O)CC(CC(O)=O)(C(O)=O)O.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O>C1COCC1.C(Cl)CCC>[F:15][C:13]1[CH:14]=[C:9]2[C:10](=[CH:11][CH:12]=1)[NH:16][C:17](=[O:18])[N:27]([CH2:26][C:25]([F:29])([F:28])[F:24])[C:1]2([OH:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a suspension of N-(2-benzoyl-4-fluorophenyl)-1H-imidazole-1-carboxamide (30.00 g, 97.00 mmol) in THF (300 mL) was added 2,2,2-trifluoroethylamine (11.53 g, 116.39 mmol). The reaction was heated to 50° C. After 19 h at 50° C., the reaction was cooled to ambient temperature. Butyl chloride (500 mL) and 10% citric acid (250 mL) were added and the reaction stirred vigorously for 40 min. The precipitate was then isolated by vacuum filtration and placed under vacuum alongside P2O5 for 16 h to give 6-fluoro-4-hydroxy-4-phenyl-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one as a yellow solid. 1H NMR (CDCl3, 400 MHz) 8.59 (s, NH); d (7.47, J=6.96 Hz, 2H, ArH); 7.36 (m, 3H, ArH); 6.99 (m, 2H, ArH); 6.79 (m, 1H, ArH); 4.39 (m, 1H, CH2); 3.56 (m, 1H, CH2); 3.23 (s, OH); MS (Electrospray): m/z 363.0 (M+Na).

Workup

temperaturethe reaction was cooled to ambient temperature
customThe precipitate was then isolated by vacuum filtration

Sources & evidence

ORD record: ord-cb17f4f1b228495ebad976dd6cb81542
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07745452B2

Linked notes

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