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

HRID 385341Notes

Reaction equation

HRID 385341 reaction equation
[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]

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-8483974fc4304cd79071cbb5ce06519f
Source dataset
uspto-grants-2013_02
Patent number
US08367863B2

Reaction notes

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