Hydrogen Peroxide → 2-[4-(2-hydroxy-1-methylethyl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide

HRID 2383541ノート

反応式

HRID 2383541 の反応式
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([NH:13][C@@H:14]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][C:24]([F:27])([F:26])[F:25])=[CH:18][N:17]=2)[CH3:15])=[O:12])=[CH:6][CH:5]=1)([CH3:3])=[CH2:2].C1C[O:31]CC1.[OH-].[Na+].OO>C(Cl)Cl.O>[OH:31][CH2:2][CH:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:10][C:11]([NH:13][C@@H:14]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][C:24]([F:27])([F:25])[F:26])=[CH:18][N:17]=2)[CH3:15])=[O:12])=[CH:8][CH:9]=1)[CH3:3]

参加物

7

反応物 4

HCID 784Hydrogen PeroxideHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 247654022-(4-isopropenylphenyl)-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide

生成物 1

HCID 247654002-[4-(2-hydroxy-1-methylethyl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide収率 42%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

A microwave vial was charged with 2-(4-isopropenylphenyl)-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide (300 mg, 0.793 mmol) and THF (500 uL). The solution was cooled to 0° C. and borane tetrahydrofuran complex (1.19 mL, 1.19 mmol) was added via syringe. The reaction was warmed to room temperature over 1.5 h., then NaOH (5M, 634 uL, 3.17 mmol) was added dropwise, followed by the slow addition of hydrogen peroxide (30 wt. % in water, 991 uL, 8.72 mmol). After stirring for 30 min, the mixture was diluted with CH2Cl2 (30 mL) and water (30 mL), and the layers were separated. The aqueous layer was washed with CH2Cl2 (2×15 mL) and the combined organic layer was dried over MgSO4, filtered, and concentrated. The resulting crude material was purified by normal phase chromatography (20-100% EtOAc/Hexanes) to give 133 mg (42%) of 2-[4-(2-hydroxy-1-methylethyl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide as a colorless oil. 1H NMR (CDCl3, 400 MHz) 8.20 (d, J=2.57 Hz, 1H), 7.21 (m, 6H), 6.69 (d, J=6.96 Hz, 1H), 5.10 (quint. J=6.96 Hz, 1H), 4.38 (q, J=8.00, 2H), 3.71 (m, 2H), 3.57 (s, 2H), 2.96 (m, 1H), 1.40 (d, J=6.67 Hz, 3H), 1.28 (d, J=6.96 Hz, 3H); MS (Electrospray): m/z 397.4 (M+H). The two diastereomers were separable by chiral HPLC under the following conditions: Column: ChiralPak AD (4.6 mm×250 mm, 10 u), Solvent: Hex/EtOH/MeOH (85/7.5/7.5), 1 mL/L diethylamine, Flow rate: 1 mL/min, Retention times: 11.3 and 12.8 min

後処理

  1. additionborane tetrahydrofuran complex (1.19 mL, 1.19 mmol) was added via syringe
  2. temperatureThe reaction was warmed to room temperature over 1.5 h.
  3. customthe layers were separated
  4. washThe aqueous layer was washed with CH2Cl2 (2×15 mL)
  5. dry with materialthe combined organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting crude material was purified by normal phase chromatography (20-100% EtOAc/Hexanes)

出典と根拠

ORDレコード
ord-1c5b4ba7bd324245af0b081a365ce347
出典データセット
uspto-grants-2012_09
特許番号
US08263627B2

反応ノート

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