Sulfuric Acid → 2-(4-Hydroxy-3-nitro-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester

HRID 385342Notes

Reaction equation

HRID 385342 reaction equation
S(=O)(=O)(O)O.[CH2:6]([O:8][C:9](=[O:26])[CH:10]([C:15]1[CH:20]=[CH:19][C:18](N)=[C:17]([C:22]([F:25])([F:24])[F:23])[CH:16]=1)[CH2:11][CH:12]([CH3:14])[CH3:13])[CH3:7].[N:27]([O-:29])=[O:28].[Na+].NC(N)=[O:33]>O.C(OCC)C>[CH2:6]([O:8][C:9](=[O:26])[CH:10]([C:15]1[CH:16]=[C:17]([C:22]([F:25])([F:24])[F:23])[C:18]([OH:33])=[C:19]([N+:27]([O-:29])=[O:28])[CH:20]=1)[CH2:11][CH:12]([CH3:14])[CH3:13])[CH3:7]

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 1176UreaHCID 23668193Sodium Nitrite2×HCID 579955332-(4-Amino-3-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester

Product 1

HCID 579955452-(4-Hydroxy-3-nitro-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl esterYield 31%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

To sulfuric acid (95-98%, 20.0 mL) was added 2-(4-amino-3-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester (6.06 g, 20.0 mmol). The mixture was cooled to 0° C. and water (30.0 mL) was added dropwise. A solution of NaNO2 (1.66 g, 24.0 mmol) in water (12 mL) was added dropwise and the mixture was stirred for additional 20 min. A few crystals of urea were added to decompose any excess NaNO2. A solution of cupric nitrate (466 g, 2.00 mol) in water (880 mL) was added, followed by addition of Cu2O (2.86 g, 20.0 mmol). The mixture was stirred for 5 min and diethyl ether (1 L) was added. The organic extract was washed with brine (500 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica-gel flash chromatography eluting with heptane/ethyl acetate (20:1) to give 2-(4-hydroxy-3-nitro-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester (2.20 g, 31%) as a yellow oil: HRMS (DIP-CI-MS): calcd for C15H19NO5F3 (M+H)+: 350.1215, found 350.1240; 1H NMR (300 MHz, CDCl3): δ 11.13 (s, 1H), 8.29 (s, 1H), 7.90 (s, 1H), 4.15 (m, 2H), 3.69 (t, 1H, J=7.8 Hz), 2.00 (m, 1H), 1.62 (m, 1H), 1.47 (m, 1H), 1.25 (t, 3H, J=7.2 Hz), 0.94 (d, 3H, J=6.3 Hz), 0.93 (d, 3H, J=6.6 Hz); 13C NMR (75 MHz, CDCl3): δ 172.75, 152.45, 134.67 (q, J=5 Hz), 134.29, 131.40, 127.90, 122.35, (q, J=271 Hz), 121.42 (q, J=32 Hz), 61.51, 48.76, 42.76, 26.23, 22.60, 22.42, 14.32.

Workup

  1. stirringThe mixture was stirred for 5 min
  2. extractionThe organic extract
  3. washwas washed with brine (500 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica-gel flash chromatography
  7. washeluting with heptane/ethyl acetate (20:1)

Sources & evidence

ORD record
ord-f0f562f668924075a01d7028cd173b5f
Source dataset
uspto-grants-2013_02
Patent number
US08367863B2

Reaction notes

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