Ethanol → Ethyl 3-ethoxy-2-nitrobut-2-enoate

HRID 1508326Notes

Reaction equation

HRID 1508326 reaction equation
ClC1C(F)=C(N[C:9]([CH3:19])=[C:10]([N+:16]([O-:18])=[O:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12])C=CC=1.[N+]([CH2:24][C:25](OCC)=[O:26])([O-])=O.C(C(CC)(CC)C([O-])([O-])[O-])C.C(O)C>C1(C)C=CC=CC=1>[CH2:25]([O:26][C:9]([CH3:19])=[C:10]([N+:16]([O-:18])=[O:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH3:24]

Participants

6

Reactant 4

HCID 702EthanolHCID 69379Ethyl nitroacetateHCID 21875354TriethylorthoaceateHCID 89405783HCID 89405783, compound

Product 1

HCID 71382919Ethyl 3-ethoxy-2-nitrobut-2-enoate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Intermediate 24A1. Ethyl 3-((3-chloro-2-fluorophenyl)amino)-2-nitrobut-2-enoate: Using a modified procedure described by Gomez-Sanchez. (Reference: Gomez-Sanchez, A. et al., Anales De Quimica, 81(2):139 (1985).) A clear, faint yellow solution of ethyl nitroacetate (4.17 ml, 37.6 mmol) and triethylorthoacetate (6.93 mL, 37.6 mmol) in toluene (9.39 mL) was heated to 110° C. A Dean-Stark trap was used to azeotrope the ethanol. Approximately every 30 min, the solvent was removed from the Dean-Stark and additional toluene (6 mL) was added to the reaction flask. Over the course of the reaction the color became a clear, dull yellow color. After 7.5 h, the reaction was stopped and it was cooled to rt. Excess solvent and starting materials were removed by distillation (5 mm Hg at 100° C.) leaving ethyl 3-ethoxy-2-nitrobut-2-enoate (5.46 g) as an orange liquid. An orange solution of 3-chloro-2-fluoroaniline (5.86 g, 40.2 mmol) and ethyl 3-ethoxy-2-nitrobut-2-enoate (5.45 g, 26.8 mmol) in ethanol (13.41 mL) was stirred at rt. After 7 h, the reaction was stopped and concentrated to give an orange oil. The orange oil was diluted with EtOAc and washed with 1.0 N HCl (2×), saturated NaHCO3, brine, dried over sodium sulfate, filtered and concentrated to give an orange oil. Purification by normal phase chromatography gave Intermediate 24A1 (2.90 g, 36%) as a viscous orange-yellow oil. 1H NMR indicated a 1:1 E:Z mixture. MS(ESI) m/z: 325.0 (M+H)+. 1H NMR (500 MHz, CDCl3) δ 11.54 (br. s., 1H), 10.77 (br. s., 1H), 7.50-7.45 (m, 1H), 7.44-7.38 (m, 1H), 7.24-7.12 (m, 4H), 4.39 (q, J=7.2 Hz, 2H), 4.34 (q, J=7.2 Hz, 2H), 2.15 (d, J=1.4 Hz, 3H), 2.12 (d, J=1.4 Hz, 3H), 1.39 (t, J=7.2 Hz, 3H), 1.36 (t, J=7.0 Hz, 3H).

Workup

  1. customthe solvent was removed from the Dean-Stark and additional toluene (6 mL)
  2. additionwas added to the reaction flask
  3. customOver the course of the reaction the color
  4. waitAfter 7.5 h
  5. customwere removed by distillation (5 mm Hg at 100° C.)

Sources & evidence

ORD record
ord-a9c2066d07784674921c898d2a4f9c91
Source dataset
uspto-grants-2015_12
Patent number
US09221818B2

Reaction notes

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