Hydrochloric Acid → N-(1-ethyl-1H-pyrazol-5-yl)-2-(2-formyl-3-hydroxyphenoxy)-N-isopropylacetamide

HRID 1770808Notes

Reaction equation

HRID 1770808 reaction equation
[CH2:1]([N:3]1[C:7]([N:8]([CH:25]([CH3:27])[CH3:26])[C:9](=[O:24])[CH2:10][O:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18]COC)[C:13]=2[CH:22]=[O:23])=[CH:6][CH:5]=[N:4]1)[CH3:2].Cl.C(=O)(O)[O-].[Na+]>C1COCC1>[CH2:1]([N:3]1[C:7]([N:8]([CH:25]([CH3:26])[CH3:27])[C:9](=[O:24])[CH2:10][O:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([OH:18])[C:13]=2[CH:22]=[O:23])=[CH:6][CH:5]=[N:4]1)[CH3:2]

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 516892Sodium BicarbonateHCID 118072802N-(1-ethyl-1H-pyrazol-5-yl)-2-(2-formyl-3-(methoxymethoxy)phenoxy)-N-isopropylacetamide

Product 1

HCID 91758735N-(1-ethyl-1H-pyrazol-5-yl)-2-(2-formyl-3-hydroxyphenoxy)-N-isopropylacetamideYield 53.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

N-(1-Ethyl-1H-pyrazol-5-yl)-2-(2-formyl-3-(methoxymethoxy)phenoxy)-N-isopropylacetamide (0.38 g, 1.01 mmol) was dissolved in THF (10 ml), purged with N2 gas and stirred in an ice bath. HCl (concentrated, 0.34 ml, 4.05 mmol) was slowly added and the solution stirred to 25° C. More HCl (0.3 ml) was added over 4 h with warming (40° C.) to reach completion of reaction. 10% Sodium bicarbonate solution (20 ml) was added and the mixture was extracted with ethyl acetate (3×75 ml). The combined organic phases were washed with a saturated aqueous sodium chloride solution (50 ml) and dried over sodium sulfate. After evaporation the resulting solid was purified by silica gel chromatography (5-80% ethyl acetate/hexanes) to give 0.179 g (53%) of N-(1-ethyl-1H-pyrazol-5-yl)-2-(2-formyl-3-hydroxyphenoxy)-N-isopropylacetamide as a white solid. 1H NMR (400 MHz, CDCl3) δ 11.90 (s, 1H), 10.35 (s, 1H), 7.50 (s, 1H), 7.43 (t, J=8.43 Hz, 1H), 6.67 (d, J=8.53 Hz, 1H), 6.39 (d, J=8.27 Hz, 1H), 6.32-6.27 (m, 1H), 6.12 (d, J=7.30 Hz, 1H), 5.65 (s, 1H), 4.25-4.13 (m, 3H), 1.46 (t, J=7.23 Hz, 3H), 1.22 (d, J=6.54 Hz, 3H), 1.14 (d, J=6.51 Hz, 3H). MS (ESI) m/z 332 [M+H]+. MP 179-182° C.

Workup

  1. custompurged with N2 gas
  2. stirringthe solution stirred to 25° C
  3. customcompletion of reaction
  4. extractionthe mixture was extracted with ethyl acetate (3×75 ml)
  5. washThe combined organic phases were washed with a saturated aqueous sodium chloride solution (50 ml)
  6. dry with materialdried over sodium sulfate
  7. customAfter evaporation the resulting solid
  8. customwas purified by silica gel chromatography (5-80% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-0d2a0f10ae6f413fae0052dfd36a2235
Source dataset
uspto-grants-2016_02
Patent number
US09248199B2

Reaction notes

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