Water → 2-(4-Amino-3-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester

HRID 1183608ノート

反応式

HRID 1183608 の反応式
[CH2:1]([O:3][C:4](=[O:23])[CH:5]([C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-])=O)=[C:12]([C:19]([F:22])([F:21])[F:20])[CH:11]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])[CH3:2].[Sn](Cl)Cl.O>C(O)C>[CH2:1]([O:3][C:4](=[O:23])[CH:5]([C:10]1[CH:15]=[CH:14][C:13]([NH2:16])=[C:12]([C:19]([F:21])([F:20])[F:22])[CH:11]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])[CH3:2]

参加物

5

反応物 3

HCID 962WaterHCID 24479Stannous ChlorideHCID 579955184-Methyl-2-(4-nitro-3-trifluoromethyl-phenyl)-pentanoic acid ethyl ester

生成物 1

HCID 579955332-(4-Amino-3-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester収率 89.2%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

A suspension of 4-methyl-2-(4-nitro-3-trifluoromethyl-phenyl)-pentanoic acid ethyl ester (38.3 g, 115 mmol), tin (II) chloride (87.2 g, 460 mmol) and water (16.6 g, 920 mmol) in ethanol (500 mL) was heated at reflux for four hours. The reaction mixture was concentrated under reduced pressure; the residue was treated with ethyl acetate (300 mL) and aqueous NaOH solution (1 N, 2.5 L). The aqueous layer was extracted with ethyl acetate (3×600 mL). The combined organic layers were washed with brine (1 L), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica-gel flash chromatography eluting with heptane/ethyl acetate (10:1) to give 2-(4-amino-3-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester (31.1 g, 89%) as a yellow oil: 1H NMR (300 MHz, CDCl3): δ 7.35 (d, 1H, J=2.1 Hz), 7.27 (dd, 1H, J=8.4, 2.1 Hz), 6.69 (d, 1H, J=8.4 Hz), 4.10 (m, 4H), 3.54 (t, 1H, J=7.8 Hz), 1.91 (m, 1H), 1.58 (m, 1H), 1.44 (m, 1H), 1.21 (t, 3H, J=6.9 Hz), 0.90 (d, 3H, J=6.6 Hz), 0.89 (d, 3H, J=6.6 Hz); 13C NMR (75 MHz, CDCl3): δ 174.14, 143.45, 132.22, 128.58, 125.91 (q, J=4 Hz), 124.80 (q, J=271 Hz), 117.35, 113.60 (q, J=29 Hz), 60.60, 48.54, 42.35, 25.77, 22.46, 22.18, 14.04.

後処理

  1. temperaturewas heated
  2. temperatureat reflux for four hours
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additionthe residue was treated with ethyl acetate (300 mL) and aqueous NaOH solution (1 N, 2.5 L)
  5. extractionThe aqueous layer was extracted with ethyl acetate (3×600 mL)
  6. washThe combined organic layers were washed with brine (1 L)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica-gel flash chromatography
  10. washeluting with heptane/ethyl acetate (10:1)

出典と根拠

ORDレコード
ord-6eacab330d1f4ac28d568f81f583574a
出典データセット
uspto-grants-2014_03
特許番号
US08664249B2

反応ノート

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