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

HRID 518098노트

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HRID 518098 반응식
C([N:8]1[CH2:14][C:13]2[N:15]=[CH:16][C:17]([O:19][C@@H:20]([CH:22]3[CH2:24][CH2:23]3)[CH3:21])=[N:18][C:12]=2[O:11][CH2:10][CH2:9]1)C1C=CC=CC=1.[Cl:25]C(OC(Cl)C)=O>C1(C)C=CC=CC=1>[ClH:25].[CH:22]1([C@H:20]([O:19][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)[CH3:21])[CH2:24][CH2:23]1

참가 물질

4

반응물 2

HCID 5213051-Chloroethyl chloroformateHCID 669931558-benzyl-3-[(1R)-1-cyclopropylethoxy]-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine

생성물 1

HCID 669931263-[(1R)-1-cyclopropylethoxy]-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine hydrochloride수율 3%

시약·촉매·용매 1

HCID 1140Toluene용매

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온도
90 °C

실험 절차

To a solution of 8-benzyl-3-[(1R)-1-cyclopropylethoxy]-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine (32.9 mg) in toluene (3 mL) was added 1-chloroethyl chloroformate (0.11 mL), and the mixture was stirred at 90° 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 1 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 (0.45 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 (8.6 mg, 3%) as colorless crystals.

후처리

  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 1 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 1 N hydrochloric acid (0.45 mL)
  13. concentrationthe mixture was concentrated under reduced pressure
  14. customThe obtained crude crystals
  15. customwere purified by recrystallization (ethanol-diisopropyl ether)

출처 및 근거

ORD 기록
ord-106e7f0011974b748511f4d3f4207d1f
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115139B2

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