Potassium Carbonate → (2R,5R)-5-(2-Fluoro-5-nitrophenyl)-2,5-dimethyl-2-(trifluoromethyl)-5,6-dihydro-2H-1,4-oxazin-3-amine

HRID 39239Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@:8]1([CH3:20])[CH2:13][O:12][C@@:11]([CH3:18])([C:14]([F:17])([F:16])[F:15])[C:10]([NH2:19])=[N:9]1.[N+:21]([O-])([O-:23])=[O:22].[K+].C([O-])([O-])=O.[K+].[K+]>OS(O)(=O)=O.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N+:21]([O-:23])=[O:22])=[CH:4][C:3]=1[C@:8]1([CH3:20])[CH2:13][O:12][C@@:11]([CH3:18])([C:14]([F:15])([F:16])[F:17])[C:10]([NH2:19])=[N:9]1

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of (2R,5R)-5-(2-fluoro-phenyl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine (1.035 g, 3.57 mmol) in H2SO4 (6 ml) was added in portions KNO3 (0.379 g, 3.74 mmol) under ice-water cooling. The reaction mixture was stirred for 2 h at 25° C., diluted with water and basified with K2CO3 under cooling. The product was extracted with EtOAc. Combined extracts were washed with saturated NaHCO3 solution and brine, dried over MgSO4, filtered and concentrated. Purification via chromatography on silica gel (hexane-EtOAc 4:1 to 1:1 containing 0.05% NEt3) gave the title compound as a light yellow oil: TLC (hexane-EtOAc 1:1): Rf=0.50; UPLC RtH5=0.749 min; ESIMS: 336 [(M+H)+]; 1H NMR (360 MHz, CDCl3): δ 8.48 (dd, 1H), 8.14 (m, 1H), 7.15 (dd, 1H), 4.20 (br s, 2H), 4.04 (dd, 1H), 3.91 (dd, 1H), 1.54 (s, 3H), 1.49 (s, 3H).

Workup

temperatureunder cooling
extractionThe product was extracted with EtOAc
washCombined extracts were washed with saturated NaHCO3 solution and brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
customPurification via chromatography on silica gel (hexane-EtOAc 4:1 to 1:1 containing 0.05% NEt3)

Sources & evidence

ORD record: ord-1df2bf46d9984cfb8ca318e66c1430b6
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08524897B2

Reaction notes

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