Hydrochloric Acid → HCID 178516531, compound

HRID 347998Notes

Reaction equation

HRID 347998 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[C:10]([NH2:13])[NH:11][N:12]=1.[Na].[CH:15]([CH2:17][C:18](OCC)=O)=[O:16].Cl>C(O)C.O.O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[C:10]2[NH:13][CH:18]=[CH:17][C:15](=[O:16])[N:11]2[N:12]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 86593876Sodium ethyl formylacetate2×HCID 178507276HCID 178507276, compound

Product 1

HCID 178516531HCID 178516531, compoundYield 98%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-(2-chlorophenyl)-2H-pyrazol-3-ylamine (I-1A-1a; 287 g, 1.48 mol) and ethyl formylacetate sodium salt (517 g, 3.74 mol) in ethanol (12 L) was heated at reflux for 6 hours. Additional ethyl formylacetate sodium salt (100 g, 0.72 mol) was added, and the reaction was heated at reflux for an additional 2 hours. After cooling to room temperature, the reaction was concentrated, in vacuo, to give an amber oil. The residue was redissolved in water (2 L) and then adjusted to pH 8 by dropwise addition of concentrated aqueous HCl. The solid precipitate that formed was isolated by vacuum filtration. This material was suspended in tetrahydrofuran (3 liters) and then stirred overnight. The solid was isolated by vacuum filtration and then dried, in vacuo, to afford I-1A-1b as an off-white solid (356 g, 98%): +APcI MS (M+1) 246.2; 1H NMR (400 MHz, DMSO-d6) δ 7.89 (d, J=7.5 Hz, 1H), 7.85–7.82 (m, 1H), 7.58–7.53 (m, 1H), 7.46–7.41 (m, 2H), 6.58 (s, 1H), 5.71 (d, J=7.1 Hz, 1H).

Workup

  1. temperatureat reflux for 6 hours
  2. temperaturethe reaction was heated
  3. temperatureat reflux for an additional 2 hours
  4. concentrationthe reaction was concentrated, in vacuo
  5. customto give an amber oil
  6. customThe solid precipitate that formed
  7. customwas isolated by vacuum filtration
  8. customThe solid was isolated by vacuum filtration
  9. customdried, in vacuo

Sources & evidence

ORD record
ord-38b6ed8e5bdd421182a7cb89da53dbc9
Source dataset
uspto-grants-2007_02
Patent number
US07176210B2

Reaction notes

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