1,4-Dioxane → Methyl 4-bromo-7,7-dimethyl-9-oxo-5,6,7,8,9,10-hexahydroacridine-1-carboxylate

HRID 521399

Reaction equation

O[C:2]1[CH2:7][CH2:6][C:5]([CH3:9])([CH3:8])[CH2:4][C:3]=1[C:10]([O:12]C)=O.[NH2:14][C:15]1[CH:16]=[C:17]([CH:22]=[CH:23][C:24]=1[Br:25])[C:18]([O:20][CH3:21])=[O:19].O1CCOCC1>O>[Br:25][C:24]1[C:15]2[NH:14][C:2]3[CH2:7][CH2:6][C:5]([CH3:8])([CH3:9])[CH2:4][C:3]=3[C:10](=[O:12])[C:16]=2[C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:22][CH:23]=1

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of methyl 2-hydroxy-5,5-dimethylcyclohex-1-enecarboxylate (26 g, 0.141 mol), methyl 3-amino-4-bromobenzoate (25 g, 0.109 mol), polyphosphoric acid (220 g) and dioxane (220 mL) was heated at 130° C. for 5 hours. After cooling, the mixture was diluted with water. The resulting precipitate was collected by filtration and dried. The solid was suspended in methanol (400 mL), and TMSCl (90 mL) was added. The mixture was stirred at reflux for 5 hours, concentrated and treated with water (80 mL), extracted with ethyl acetate (250 mL). The organic layer was separated, concentrated and recrystallized with methanol to afford desired compound (10.6 g, 27%). 1H NMR (DMSO-d6) δ 10.32 (s, 1H), 7.98 (d, 1H, J=7.2 Hz), 7.10 (d, 1H, J=7.2 Hz), 3.80 (s, 3H), 2.90 (t, 2H, J=6.6 Hz), 2.22 (s, 2H), 1.56 (t, 2H, J=6.6 Hz), and 0.97 (s, 6H). MS (ESI) m/e [M+1]+364.

Workup

temperatureAfter cooling
filtrationThe resulting precipitate was collected by filtration
customdried
additionTMSCl (90 mL) was added
temperatureat reflux for 5 hours
concentrationconcentrated
additiontreated with water (80 mL)
extractionextracted with ethyl acetate (250 mL)
customThe organic layer was separated
concentrationconcentrated
customrecrystallized with methanol

Sources & evidence

ORD record: ord-63c433ca5a9c4c4d9a7a233410442823
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328111B2

Linked notes

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