Acetyl chloride → Acetic acid 7-allyl-1H-indazol-6-yl ester

HRID 1815938Notes

Reaction equation

HRID 1815938 reaction equation
[CH2:1]([C:4]1[C:5]([OH:13])=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][N:10]=[CH:9]2)[CH:2]=[CH2:3].C(N(CC)CC)C.[C:21](Cl)(=[O:23])[CH3:22]>C1COCC1>[CH2:1]([C:4]1[C:5]([O:13][C:21](=[O:23])[CH3:22])=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][N:10]=[CH:9]2)[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 6367Acetyl chloride3×HCID 8471TriethylamineHCID 1358436477-Allyl-1H-indazol-6-ol

Product 1

HCID 69566045Acetic acid 7-allyl-1H-indazol-6-yl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of the product from Step B (6.35 g, 37 mmol) in THF (100 mL) containing triethylamine (7.6 ml, 55 mmol) was stirred for 5 minutes at ambient temperature, cooled to 0° C. (ice bath), and acetyl chloride (2.63 mL, 37 mmol) was added. The mixture was stirred at 0° C. for 2 hours, additional acetyl chloride (0.26 mL, 3.7 mmol) was added, and the mixture stirred for 10 min at which point another portion of acetyl chloride (0.26 ml, 3.7 mmol) was added and stirring continued for 15 min. The reaction was quenched with triethyl amine (1 mL) and saturated aqueous sodium bicarbonate (100 mL) and extracted with ethyl acetate (100 mL). The extract was dried (MgSO4) and evaporated to an oil (9.27 g) which was purified by chromatography (silica, 10% to 50% EtOAc/hexane) to give a white solid, (3.50 g, 44%): LC/MS (+APCI) m/z 217 (M+H).

Workup

  1. additionwas added
  2. stirringThe mixture was stirred at 0° C. for 2 hours
  3. additionwas added
  4. stirringstirring
  5. waitcontinued for 15 min
  6. customThe reaction was quenched with triethyl amine (1 mL) and saturated aqueous sodium bicarbonate (100 mL)
  7. extractionextracted with ethyl acetate (100 mL)
  8. dry with materialThe extract was dried (MgSO4)
  9. customevaporated to an oil (9.27 g) which
  10. customwas purified by chromatography (silica, 10% to 50% EtOAc/hexane)
  11. customto give a white solid, (3.50 g, 44%)

Sources & evidence

ORD record
ord-040a4425ba55440091d6a07ecc85b2fc
Source dataset
uspto-grants-2005_04
Patent number
US06881749B2

Reaction notes

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