Barbituric Acid → rel-(2R,4R,4aR)-1,2,4,4a-tetrahydro-4-methyl-8-nitro-2-(trifluoromethyl)spiro[[1,4]oxazino[4,3-a]quinoline-5(6H), 5'(2'H)-pyrimidine]-2',4',6'(1'H,3'H)-trione

HRID 1966324Notes

Reaction equation

[CH3:1][C@H:2]1[O:7][C@@H:6]([C:8]([F:11])([F:10])[F:9])[CH2:5][N:4]([C:12]2[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][C:13]=2[CH:14]=O)[CH2:3]1.[NH:23]1[C:30](=[O:31])[CH2:29][C:27](=[O:28])[NH:26][C:24]1=[O:25]>CO>[CH3:1][C@@H:2]1[C@H:3]2[C:29]3([CH2:14][C:13]4[C:12]([N:4]2[CH2:5][C@H:6]([C:8]([F:10])([F:9])[F:11])[O:7]1)=[CH:19][CH:18]=[C:17]([N+:20]([O-:22])=[O:21])[CH:16]=4)[C:27](=[O:28])[NH:26][C:24](=[O:25])[NH:23][C:30]3=[O:31]

Participants

Conditions

Temperature: 80 °C

Procedure

2-[cis-2-methyl-6-(trifluoromethyl)morpholin-4-yl]-5-nitrobenzaldehyde (212 mg, 0.67 mol) is combined with barbituric acid (95 mg, 0.67 mmol, Aldrich) in a vial with MeOH (3 mL). The sealed reaction is heated to 80° C. on a shaker block for 21 hours and then the solvent is removed by rotary evaporation. The product is purified on a Biotage Flash 25M+ using a 26 minute linear gradient of 2.5%-10% MTBE in CH2Cl2 eluent. The product is dried under vacuum yielding a yellow-orange solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.01, 2.93, 3.46, 3.66, 3.73, 4.04, 4.40, 4.48, 7.10, 7.88, 8.01, 11.63, 11.94.

Workup

customThe sealed reaction
customthe solvent is removed by rotary evaporation
customThe product is purified on a Biotage Flash 25M+
customThe product is dried under vacuum
customyielding a yellow-orange solid

Sources & evidence

ORD record: ord-9f41eea4ceb7449ca8143b3e7c86be62
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08420646B2

Reaction notes

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