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

HRID 2188700ノート

反応式

HRID 2188700 の反応式
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

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
90 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-9bf0576a8a67467990858e03196cb11b
出典データセット
uspto-grants-2012_12
特許番号
US08324201B2

反応ノート

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