1-Chloroethyl chloroformate → 3-(Cyclopent-1-en-1-yl)-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine hydrochloride

Temperature

90 °C

To a solution of 8-benzyl-3-(cyclopent-1-en-1-yl)-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine (99 mg) in toluene (1 mL) was added 1-chloroethyl chloroformate (0.038 mL), and the mixture was stirred at 90° C. for 4 hr. 1-Chloroethyl chloroformate (0.038 mL) was further added, and the mixture was stirred at 90° C. for 1 hr. The reaction mixture was cooled to room temperature, and concentrated. To the obtained residue was added methanol (1 mL), and the mixture was stirred at 60° C. for 0.5 hr. The reaction mixture was cooled to room temperature, and concentrated. The concentrate was diluted with ethyl acetate, and washed with saturated aqueous sodium hydrogen carbonate, water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (solvent gradient; 10→100% ethyl acetate/hexane). To a solution of the obtained oil in methanol (1 mL) was added 1 N hydrochloric acid (0.18 ml), and the mixture was concentrated under reduced pressure. The obtained crude crystals were purified by recrystallization (ethanol-diisopropyl ether) to give the title compound (41.1 mg, 50%) as colorless crystals.

1. stirringthe mixture was stirred at 90° C. for 1 hr
2. temperatureThe reaction mixture was cooled to room temperature
3. concentrationconcentrated
4. additionTo the obtained residue was added methanol (1 mL)
5. stirringthe mixture was stirred at 60° C. for 0.5 hr
6. temperatureThe reaction mixture was cooled to room temperature
7. concentrationconcentrated
8. additionThe concentrate was diluted with ethyl acetate
9. washwashed with saturated aqueous sodium hydrogen carbonate, water and saturated brine
10. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
11. concentrationconcentrated under reduced pressure
12. customThe obtained residue was purified by basic silica gel column chromatography (solvent gradient; 10→100% ethyl acetate/hexane)
13. additionTo a solution of the obtained oil in methanol (1 mL) was added 1 N hydrochloric acid (0.18 ml)
14. concentrationthe mixture was concentrated under reduced pressure
15. customThe obtained crude crystals
16. customwere purified by recrystallization (ethanol-diisopropyl ether)

ORD record

ord-4dde99eb030743239f22afe3208657fe

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08318722B2