N-benzylhydroxylamine hydrochloride → 2-Benzyl-5-(2,5-difluorophenyl)-3-phenylisoxazolidin-5-ol

HRID 15114ノート

反応式

HRID 15114 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9](=[O:18])/[CH:10]=[CH:11]/[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.Cl.[CH2:20]([NH:27][OH:28])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C(O)C>[CH2:20]([N:27]1[CH:11]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:10][C:9]([C:3]2[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=2[F:1])([OH:18])[O:28]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

参加物

4

反応物 2

HCID 11332622N-benzylhydroxylamine hydrochloride2 回HCID 59341269(2E)-1-(2,5-difluorophenyl)-3-phenylprop-2-en-1-one

生成物 1

HCID 575391232-Benzyl-5-(2,5-difluorophenyl)-3-phenylisoxazolidin-5-ol

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

A mixture of (2E)-1-(2,5-difluorophenyl)-3-phenylprop-2-en-1-one (1-1) (500 mg, 2.05 mmol, 1 equiv) and N-benzylhydroxylamine hydrochloride (327 mg, 2.05 mmol, 1.00 equiv) was heated at reflux in ethanol (10 mL) for 4 h. Additional N-benzylhydroxylamine hydrochloride (327 mg, 2.05 mmol, 1.00 equiv) was added and the mixture was heated at reflux for 16 h. The reaction mixture was partitioned between saturated sodium bicarbonate solution (50 mL) and ethyl acetate (2×50 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (silica, 100% hexanes initially, grading to 100% EtOAc) to give 2-benzyl-5-(2,5-difluorophenyl)-3-phenylisoxazolidin-5-ol (1-2); LRMS m/z (M+H) 368.3 found, 368.1 required. Methanesulfonyl chloride (0.093 uL, 1.20 mmol, 1.11 equiv) was added to a solution of (1-2) (400 mg, 1.09 mmol, 1 equiv) and triethylamine (0.455 mL, 3.27 mmol, 3.00 equiv) in dichloromethane (30 mL) at 0° C. and the resultant mixture was warmed to 23° C. and stirred for 30 min. The reaction mixture was partitioned between saturated sodium bicarbonate solution (50 mL) and dichloromethane (2×50 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (silica, 100% hexanes initially, grading to 100% EtOAc) to give 2-benzyl-5-(2,5-difluorophenyl)-3-phenyl-2,3-dihydroisoxazole (1-3) as a white solid. 1H NMR (300 MHz, CDCl3) δ 7.46-7.21 (m, 11H), 7.02 (m, 2H), 5.76 (t, 1H, J=3.0 Hz), 5.12 (d, 11H, J=2.8 Hz), 4.41 (d, 1H, J=12.8 Hz), 4.10 (d, 1H, J=12.8 Hz). LRMS m/z (M+H) 350.3 found, 350.1 required.

後処理

  1. temperaturewas heated
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 16 h
  4. customThe reaction mixture was partitioned between saturated sodium bicarbonate solution (50 mL) and ethyl acetate (2×50 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography (silica, 100% hexanes initially

出典と根拠

ORDレコード
ord-2f54ed7ae4e547a59553d0fadaff22c6
出典データセット
uspto-grants-2010_06
特許番号
US07732472B2

反応ノート

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