Sodium Hydroxide → 1-Amino-6-cyclopropyl-4-(4-trifluoromethyl-phenyl)-1H-pyridin-2-one

HRID 558629Notes

Reaction equation

[CH:1]1([C:4]2[NH:9][C:8](=[O:10])[CH:7]=[C:6]([C:11]3[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=3)[CH:5]=2)[CH2:3][CH2:2]1.[OH-].[Na+].[NH2:23]OS(O)(=O)=O>C1COCC1.O>[NH2:23][N:9]1[C:4]([CH:1]2[CH2:2][CH2:3]2)=[CH:5][C:6]([C:11]2[CH:12]=[CH:13][C:14]([C:17]([F:20])([F:18])[F:19])=[CH:15][CH:16]=2)=[CH:7][C:8]1=[O:10]

Participants

Conditions

Temperature: 23 °C

Procedure

To a solution of 6-cyclopropyl-4-(4-trifluoromethyl-phenyl)-1H-pyridin-2-one (example C.28 step 2) (4.19 g, 15.0 mmol) in THF (225 mL) and 1M NaOH (90.0 mL, 90.0 mmol) was added dropwise a solution of hydroxylamine-O-sulfonic acid (HOSA) (95%, 5.36 g, 45.0 mmol) in H2O (60 mL) at 0° C. The reaction mixture was stirred at 23° C. for 20 h (76% conversion). Added again at 0° C. 3N NaOH (30 mL, 30.0 mmol) and then hydroxylamine-O-sulfonic acid (HOSA) (95%, 5.36 g, 45.0 mmol) and the reaction mixture was stirred at 23° C. for 3 days (88% conversion). Poured into ice water, extracted with EtOAc, washed the organic layers with brine, dried over Na2SO4. Removal of the solvent in vacuum left a residue (5.17 g) which was purified by silica gel chromatography (400 g SiO2) to give the title compound as a light yellow solid (2.81 g, 64%). MS (ISP) 295.5 [(M+H)+]; mp 132° C.

Workup

customat 0° C
additionAdded again at 0° C
extractionextracted with EtOAc
washwashed the organic layers with brine
dry with materialdried over Na2SO4
customRemoval of the solvent in vacuum
waitleft a residue (5.17 g) which
customwas purified by silica gel chromatography (400 g SiO2)

Sources & evidence

ORD record: ord-8bb2fd35788048a9accd68225bba8a7f
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08063048B2

Reaction notes

Loading…