Hydrochloric Acid → Methyl 4-butyl-8-cyano-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate

HRID 14194

Reaction equation

Br[C:2]1[C:11]2[O:10][CH2:9][CH2:8][N:7]([CH2:12][CH2:13][CH2:14][CH3:15])[C:6]=2[CH:5]=[C:4]([C:16]([O:18][CH3:19])=[O:17])[CH:3]=1.[Cu](C#N)[C:21]#[N:22].Cl>CN1C(=O)CCC1>[CH2:12]([N:7]1[C:6]2[CH:5]=[C:4]([C:16]([O:18][CH3:19])=[O:17])[CH:3]=[C:2]([C:21]#[N:22])[C:11]=2[O:10][CH2:9][CH2:8]1)[CH2:13][CH2:14][CH3:15]

Participants

Conditions

Temperature: 175 °C

Procedure

To a flask containing methyl 8-bromo-4-butyl-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate (0.33 g) was added NMP (7 mL), followed by copper cyanide (0.18 g). The mixture was then heated to 175° C. and stirred overnight. The resulting mixture was cooled to room temperature and poured into 1 N hydrochloric acid. The acidic aqueous layer was extracted with ethyl acetate, washed with 1 N hydrochloric acid (15 mL), saturated sodium bicarbonate (15 mL), and brine, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:9 ethyl acetate/hexanes) provided 184 mg of the title compound: 1H NMR (300 MHz, CDCl3) δ 7.55, 7.43, 4.41, 3.89, 3.39, 3.31, 1.58, 1.40, 0.97.

Workup

temperatureThe resulting mixture was cooled to room temperature
extractionThe acidic aqueous layer was extracted with ethyl acetate
washwashed with 1 N hydrochloric acid (15 mL), saturated sodium bicarbonate (15 mL), and brine
dry with materialdried (magnesium sulfate)
filtrationfiltered
concentrationconcentrated under reduced pressure
customPurification by flash column chromatography (silica, 1:9 ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-c734aefb23a24984b9ddb1e684b7fdcb
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07727997B2

Linked notes

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