Benzene--cyclohexane (1/1) → 3-ethyl-5-nitro-3-pyridin-2-yl-3,4-dihydro-2H-1,4-benzoxazine

HRID 589059Notes

Reaction equation

[CH2:1]([Li])[CH3:2].C1C=CC=CC=1.C1CCCCC1.[N+:16]([C:19]1[C:24]2[N:25]=[C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=3)[CH2:27][O:28][C:23]=2[CH:22]=[CH:21][CH:20]=1)([O-:18])=[O:17]>O1CCCC1>[CH2:1]([C:26]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=2)[NH:25][C:24]2[C:19]([N+:16]([O-:18])=[O:17])=[CH:20][CH:21]=[CH:22][C:23]=2[O:28][CH2:27]1)[CH3:2]

Participants

Conditions

Temperature: -78 °C

Procedure

0.5 M Ethyl lithium in benzene-cyclohexane (1.8 mL, 0.88 mmol) was added drop-wise to a solution of 5-nitro-3-pyridin-2-yl-2H-1,4-benzoxazine (0.025 g, 0.88 mmol) in tetrahydrofuran (4 mL), cooled to −78° C. The reaction was stirred for 1 h at −78° C. and was then quenched with methanol. The reaction mixture was partitioned between ethyl acetate and water, and the organic layer was washed with brine, dried over magnesium sulfate, filtered, and concentrated to give crude product. The product was purified by FCC on silica gel eluting a hexane:ethyl acetate gradient to give 3-ethyl-5-nitro-3-pyridin-2-yl-3,4-dihydro-2H-1,4-benzoxazine as a solid (0.021 g. 84%). LCMS calculated for C15H16N3O3 (M+H)+: m/z=286.1. found: 286.0.

Workup

customwas then quenched with methanol
customThe reaction mixture was partitioned between ethyl acetate and water
washthe organic layer was washed with brine
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
customto give crude product
customThe product was purified by FCC on silica gel eluting a hexane

Sources & evidence

ORD record: ord-201ae97b463f4655806c488d4a39f5b9
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09227985B2

Reaction notes

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