Ethyl Acetoacetate → HCID 66746746, compound

HRID 1466973Notes

Reaction equation

HRID 1466973 reaction equation
[NH2:1][C:2]1[C:3]([C:19]#[N:20])=[C:4]([CH:16]=[CH:17][CH:18]=1)[O:5][CH2:6][C:7]([CH3:15])([CH3:14])[C:8]([NH:10][CH2:11][CH2:12][CH3:13])=[O:9].[C:21]([O:27][CH2:28][CH3:29])(=[O:26])[CH2:22][C:23]([CH3:25])=O.Cl[Sn](Cl)(Cl)Cl>C1(C)C=CC=CC=1>[NH2:20][C:19]1[C:3]2[C:2](=[CH:18][CH:17]=[CH:16][C:4]=2[O:5][CH2:6][C:7]([CH3:15])([CH3:14])[C:8](=[O:9])[NH:10][CH2:11][CH2:12][CH3:13])[N:1]=[C:23]([CH3:25])[C:22]=1[C:21]([O:27][CH2:28][CH3:29])=[O:26]

Participants

5

Reactant 3

HCID 8868Ethyl AcetoacetateHCID 24287Tin tetrachlorideHCID 468336623-(3-Amino-2-cyanophenoxy)-2,2-dimethyl-N-propylpropanamide

Product 1

HCID 66746746HCID 66746746, compoundYield 84.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 3-(3-amino-2-cyanophenoxy)-2,2-dimethyl-N-propylpropan-amide (Tachdjian, C. et al. PCT Int. Appl. 2008, WO 2008154221, 1.38 g, 5.0 mmol) and ethyl acetoacetate (0.66 g, 5.0 mmol) in dry toluene (150 mL) was added SnCl4 (2.61 g, 10.0 mmol) dropwise via syringe at room temperature under nitrogen. After 1 hr at room temperature, the reaction mixture was refluxed for an additional 5 hrs. The solution was cooled to room temperature and the solvent removed under reduced pressure. The residue was diluted with EtOAc, and aqueous NaOH (2N) was added at room temperature to pH>8. The solution was filtered and the organic layer separated. The aqueous layer was extracted with EtOAc (5×). The combined organic layers was washed with brine, and dried over Na2SO4. After evaporation of the solvent, the residue was purified by chromatography on silica gel (0.5% MeOH in EtOAc) to give the title compound as an off-white solid (1.63 g, 84%). 1H NMR (400 MHz, DMSO-d6) δ 0.73 (t, J=7.6 Hz, 3H), 1.25 (s, 6H), 1.32 (t, J=7.4 Hz, 3H), 1.35-1.42 (m, 2H), 2.54 (s, 3H), 3.00-3.05 (m, 2H), 4.12 (s, 2H), 4.31 (q, J=7.4 Hz, 2H), 6.87 (d, J=8.0 Hz, 1H), 7.23 (d, J=8.0 Hz, 1H), 7.50 (t, J=8.0 Hz, 1H), 7.80 (t, J=5.6 Hz, 1H), 8.08 (s, 2H). MS 388 (MH+).

Workup

  1. temperaturethe reaction mixture was refluxed for an additional 5 hrs
  2. customthe solvent removed under reduced pressure
  3. additionThe residue was diluted with EtOAc, and aqueous NaOH (2N)
  4. additionwas added at room temperature to pH>8
  5. filtrationThe solution was filtered
  6. customthe organic layer separated
  7. extractionThe aqueous layer was extracted with EtOAc (5×)
  8. washThe combined organic layers was washed with brine
  9. dry with materialdried over Na2SO4
  10. customAfter evaporation of the solvent
  11. customthe residue was purified by chromatography on silica gel (0.5% MeOH in EtOAc)

Sources & evidence

ORD record
ord-9c08ba8c7ec64f6f86fdac129c47586b
Source dataset
uspto-grants-2015_04
Patent number
US09000054B2

Reaction notes

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