1-Chloroethyl chloroformate → 3-Cyclopropyl-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine hydrochloride

HRID 518101Notes

Reaction equation

HRID 518101 reaction equation
C([N:8]1[CH2:14][C:13]2[N:15]=[CH:16][C:17]([CH:19]3[CH2:21][CH2:20]3)=[N:18][C:12]=2[O:11][CH2:10][CH2:9]1)C1C=CC=CC=1.[Cl:22]C(OC(Cl)C)=O>C1(C)C=CC=CC=1>[ClH:22].[CH:19]1([C:17]2[CH:16]=[N:15][C:13]3[CH2:14][NH:8][CH2:9][CH2:10][O:11][C:12]=3[N:18]=2)[CH2:21][CH2:20]1

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 669933158-Benzyl-3-cyclopropyl-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine

Product 1

HCID 669934443-Cyclopropyl-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine hydrochlorideYield 16%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 8-benzyl-3-cyclopropyl-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine (79.9 mg) in toluene (3 mL) was added 1-chloroethyl chloroformate (0.033 mL), and the mixture was stirred at 100° C. for 3 hr. The reaction mixture was cooled to room temperature, and concentrated. To the obtained residue was added methanol (3 mL) and the mixture was stirred at 60° C. for 2 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 0.1 N hydrochloric acid (0.6 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 (10.2 mg, 16%) as colorless crystals.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated
  3. additionTo the obtained residue was added methanol (3 mL)
  4. stirringthe mixture was stirred at 60° C. for 2 hr
  5. temperatureThe reaction mixture was cooled to room temperature
  6. concentrationconcentrated
  7. additionThe concentrate was diluted with ethyl acetate
  8. washwashed with saturated aqueous sodium hydrogen carbonate, water and saturated brine
  9. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe obtained residue was purified by basic silica gel column chromatography (solvent gradient; 10→100% ethyl acetate/hexane)
  12. additionTo a solution of the obtained oil in methanol (1 mL) was added 0.1 N hydrochloric acid (0.6 mL)
  13. concentrationthe mixture was concentrated under reduced pressure
  14. customThe obtained crude crystals
  15. customwere purified by recrystallization (ethanol-diisopropyl ether)

Sources & evidence

ORD record
ord-187fca072f8b4d539bc89998fd3f953d
Source dataset
uspto-grants-2015_08
Patent number
US09115139B2

Reaction notes

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