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

HRID 1914774Notes

Reaction equation

HRID 1914774 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 rt. was treated with pyridine (4.56 mL, 56.33 mmol) and methanesulfonyl chloride (1.31 mL) and stirred at rt. for 16 hours. The reaction mixture was concentrated in vacuo and the resulting 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 yield tert-butyl 5-(chloromethyl)-6-fluoro-1H-indazole-1-carboxylate (24G, 1.9 g; Yield=59%)

Workup

  1. customat rt
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionthe resulting 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-e705d0fd78254920862e98725b977d31
Source dataset
uspto-grants-2013_12
Patent number
US08614229B2

Reaction notes

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