Phosphorus oxychloride → ethyl 4-cyano-6,7-dihydro-1,3-dimethyl-1H-indazole-5-carboxylate

HRID 439724

Reaction equation

HRID 439724 reaction equation
[C:1]([C:3]1(O[Si](C)(C)C)[CH:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:10][CH2:9][C:8]2[N:7]([CH3:17])[N:6]=[C:5]([CH3:18])[C:4]1=2)#[N:2].P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1>[C:1]([C:3]1[C:4]2[C:5]([CH3:18])=[N:6][N:7]([CH3:17])[C:8]=2[CH2:9][CH2:10][C:11]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13])#[N:2]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 22402969ethyl 4-cyano-4,5,6,7-tetrahydro-1,3-dimethyl-4-(trimethylsilyloxy)-1H-indazole-5-carboxylate

Product 1

HCID 22402928ethyl 4-cyano-6,7-dihydro-1,3-dimethyl-1H-indazole-5-carboxylateYield 53.1%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of ethyl 4-cyano-4,5,6,7-tetrahydro-1,3-dimethyl-4-(trimethylsilyloxy)-1H-indazole-5-carboxylate (28.1 g, 0.119 mol) in pyridine is mixed with phosphorus oxychloride (43.0 mL, 0.461 mol), stirred for 5 hours at reflux temperature and concentrated in vacuo. The resultant black residue is diluted with ethyl acetate and water and treated with sodium bicarbonate to pH 6. The phases are separated, the organic phase is set aside, and the aqueous phase is extracted with ethyl acetate. The organic phases are combined, washed with aqueous sodium bicarbonate and water, dried (MgSO4) and concentrated in vacuo to give a black residue. The residue is triturated under ethyl acetate to give the title product as a tan solid (15.5 g, 52.9%), identified by 1HNMR and IR spectroscopy.

Workup

  1. temperatureat reflux temperature
  2. concentrationconcentrated in vacuo
  3. additionThe resultant black residue is diluted with ethyl acetate and water
  4. additiontreated with sodium bicarbonate to pH 6
  5. customThe phases are separated
  6. extractionthe aqueous phase is extracted with ethyl acetate
  7. washwashed with aqueous sodium bicarbonate and water
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customto give a black residue
  11. customThe residue is triturated under ethyl acetate

Sources & evidence

ORD record
ord-25104ed23134410ebadbd8b76540278c
Source dataset
uspto-grants-1996_05
Patent number
US05516751

Linked notes

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