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

반응식

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

참가 물질

반응물 4

HCID 1049Pyridine

HCID 6344Dichloromethane

HCID 31297Methanesulfonyl chloride

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

생성물 1

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

실험 절차

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%)