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

HRID 1952232Notes

Reaction equation

HRID 1952232 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 (22F, 3.0 g, 11.27 mmol) in methylene chloride (50.00 mL, 780.0 mmol) at rt. was treated with pyridine (4.56 mL, 56.33 mmol) and methanesulfonyl chloride (1.31 mL) and stirred at rt. for 16 h. 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 by chromatography (SiO2, EtOAc/Hexanes) to yield tert-butyl 5-(chloromethyl)-6-fluoro-1H-indazole-1-carboxylate (22G, 1.9 g; Yield=59%)

Workup

  1. customat rt
  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 by chromatography (SiO2, EtOAc/Hexanes)

Sources & evidence

ORD record
ord-a0ca1b37e6344f20ad5e517473174f85
Source dataset
uspto-grants-2013_03
Patent number
US08404845B2

Reaction notes

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