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

反応式

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

参加物

反応物 4

HCID 1049Pyridine

HCID 6344Dichloromethane

HCID 31297Methanesulfonyl chloride

HCID 59490881(1-Boc-6-fluoro-5-indazolyl)methanol

生成物 1

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

実験手順

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%)