Hydrogen chloride-ethyl acetate → N-{(1S)-2-[(6-{6-[2-(2,2-difluorocyclopropyl)ethoxy]-1,3-benzoxazol-2-yl}-5-fluoropyridin-3-yl)oxy]-1-methylethyl}acetamide

HRID 1026333ノート

反応式

HRID 1026333 の反応式
[F:1][C:2]1([F:36])[CH2:4][CH:3]1[CH2:5][CH2:6][O:7][C:8]1[CH:35]=[CH:34][C:11]2[N:12]=[C:13]([C:15]3[N:20]=[CH:19][C:18]([O:21][CH2:22][C@@H:23]([NH:25][C:26](=[O:32])OC(C)(C)C)[CH3:24])=[CH:17][C:16]=3[F:33])[O:14][C:10]=2[CH:9]=1.Cl.[C:38](OCC)(=O)C>C(OCC)(=O)C>[F:1][C:2]1([F:36])[CH2:4][CH:3]1[CH2:5][CH2:6][O:7][C:8]1[CH:9]=[CH:10][C:11]2[N:12]=[C:13]([C:15]3[N:20]=[CH:19][C:18]([O:21][CH2:22][C@@H:23]([NH:25][C:26](=[O:32])[CH3:38])[CH3:24])=[CH:17][C:16]=3[F:33])[O:14][C:34]=2[CH:35]=1

参加物

4

反応物 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 86666316tert-butyl {(1S)-2-[(6-{6-[2-(2,2-difluorocyclopropyl)ethoxy]-1,3-benzoxazol-2-yl}-5-fluoropyridin-3-yl)oxy]-1-methylethyl}carbamate

生成物 1

HCID 67778739N-{(1S)-2-[(6-{6-[2-(2,2-difluorocyclopropyl)ethoxy]-1,3-benzoxazol-2-yl}-5-fluoropyridin-3-yl)oxy]-1-methylethyl}acetamide

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

A mixture of tert-butyl {(1S)-2-[(6-{6-[2-(2,2-difluorocyclopropyl)ethoxy]-1,3-benzoxazol-2-yl}-5-fluoropyridin-3-yl)oxy]-1-methylethyl}carbamate (910 mg), 4 M hydrogen chloride/ethyl acetate (10 mL), and ethyl acetate (10 mL) was stirred at room temperature overnight. The mixture was concentrated under reduced pressure. The residue was mixed with pyridine (10 mL) and acetic anhydride (5 mL). The mixture was stirred at room temperature overnight. 1 M hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) and recrystallization (ethyl acetate/hexane) to give the title compound (475 mg) as white crystals.

後処理

  1. concentrationThe mixture was concentrated under reduced pressure
  2. additionThe residue was mixed with pyridine (10 mL) and acetic anhydride (5 mL)
  3. stirringThe mixture was stirred at room temperature overnight
  4. addition1 M hydrochloric acid was added
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate) and recrystallization (ethyl acetate/hexane)

出典と根拠

ORDレコード
ord-8715e989c7204ff2bc27388899033344
出典データセット
uspto-grants-2014_05
特許番号
US08729102B2

反応ノート

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