Pyridine → tert-butyl 5-(chloromethyl)-6-fluoro-1H-indazole-1-carboxylate

HRID 1098661Notes

Reaction equation

HRID 1098661 reaction equation
O[CH2:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[F:12])[N:8]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[N:7]=[CH:6]2.C(Cl)[Cl:21].N1C=CC=CC=1.CS(Cl)(=O)=O>>[Cl:21][CH2:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[F:12])[N:8]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[N:7]=[CH:6]2

Participants

5

Reactant 4

HCID 1049PyridineHCID 6344DichloromethaneHCID 31297Methanesulfonyl chlorideHCID 59490881(1-Boc-6-fluoro-5-indazolyl)methanol

Product 1

HCID 59490899tert-butyl 5-(chloromethyl)-6-fluoro-1H-indazole-1-carboxylateYield 59.2%

Procedure

A solution of tert-butyl 5-(hydroxymethyl)-6-fluoro-1H-indazole-1-carboxylate (29F, 3.0 g, 11.27 mmol) in methylene chloride (50.00 mL, 780.0 mmol) at room temperature. was treated with pyridine (4.56 mL, 56.33 mmol) and methanesulfonyl chloride (1.31 mL) and stirred at room temperature for 16 hours. The reaction mixture was concentrated in vacuo and the residue was dissolved in EtOAc (300 mL) washed with aq HCl (100 mL), brine (100 mL), dried (MgSO4), filtered, concentrated in vacuo, and purified using chromatography (SiO2, EtOAc/Hexanes) to provide tert-butyl 5-(chloromethyl)-6-fluoro-1H-indazole-1-carboxylate (24G, 1.9 g; Yield=59%)

Workup

  1. customat room temperature
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionthe residue was dissolved in EtOAc (300 mL)
  4. washwashed with aq HCl (100 mL), brine (100 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. custompurified

Sources & evidence

ORD record
ord-571f9593b6994a0d9d14b55cacfe5b72
Source dataset
uspto-grants-2012_03
Patent number
US08143305B2

Reaction notes

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