Hydrochloric Acid → ethyl (2E)-2-chloro-2-[[5-fluoro-2-[(E)-3-phenylprop-2-enoxy]phenyl]hydrazinylidene]acetate

HRID 1867262Notes

Reaction equation

HRID 1867262 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:9][CH2:10]/[CH:11]=[CH:12]/[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:6]([CH:8]=1)[NH2:7].Cl.[CH2:20]([O:22][C:23](=[O:29])[CH:24]([Cl:28])C(C)=O)[CH3:21].[N:30]([O-])=O.[Na+].CC([O-])=O.[Na+]>CC(O)=O.O>[Cl:28]/[C:24](=[N:30]/[NH:7][C:6]1[CH:8]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=1[O:9][CH2:10]/[CH:11]=[CH:12]/[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)/[C:23]([O:22][CH2:20][CH3:21])=[O:29]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 11858Ethyl 2-chloroacetoacetateHCID 517045Sodium AcetateHCID 23668193Sodium NitriteHCID 684510525-Fluoro-2-{[(2E)-3-phenylprop-2-enyl]oxy}aniline

Product 1

HCID 89029529ethyl (2E)-2-chloro-2-[[5-fluoro-2-[(E)-3-phenylprop-2-enoxy]phenyl]hydrazinylidene]acetate

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
-5 °C

Procedure

5-Fluoro-2-{[(2E)-3-phenylprop-2-enyl]oxy}aniline (5-2, 2.19 g, 9.0 mmol) was suspended in a 1.2 N solution of HCl in 60% aq. AcOH (18 mL) and treated with ethyl-2-chloroacetoacetate (3.7 mL, 27 mmol). The mixture was cooled to −5° C. in a NaCl/ice bath and a 1.4 M solution of NaNO2 (12.6 mmol) in water was added dropwise under vigorous stirring. Upon completion of the addition, the mixture was adjusted to pH=4 with NaOAc and stirred to 25° C. for 2 h. The organics were extracted with CH2Cl2 (3×50 mL), dried (Na2SO4) and evaporated under reduced pressure. The crude was recrystallized from EtOAc/hexanes to give ethyl (2E)-chloro[(5-fluoro-2-{[(2E)-3-phenylprop-2-enyl]oxy}phenyl)hydrazono]ethanoate (5-3) as a brown solid. 1H NMR (300 MHz, CDCl3) δ 8.86 (s, 1H), 7.41 (d, J=7.3 Hz, 1H), 7.32 (m, 5H), 6.87 (dd, J=9.0, 4.7 Hz, 1H), 6.79 (d, J=15.9 Hz, 1H), 6.64 (app dt, J=8.3, 2.9 Hz, 1H), 6.40 (app dt, J=15.9, 5.5 Hz, 1H), 4.76 (d, J=5.2 Hz, 2H), 4.39 (q, J=7.0 Hz, 2H), 1.41 (t, J=7.0 Hz, 3H); MS (M+H+, C19H18ClFN2O3) 377.1 found 377.8 required.

Workup

  1. additionUpon completion of the addition
  2. extractionThe organics were extracted with CH2Cl2 (3×50 mL)
  3. dry with materialdried (Na2SO4)
  4. customevaporated under reduced pressure
  5. customThe crude was recrystallized from EtOAc/hexanes

Sources & evidence

ORD record
ord-bb61d064b73c43b0b331443cef8f1bf1
Source dataset
uspto-grants-2009_12
Patent number
US07632833B2

Reaction notes

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