Benzoyl Peroxide → Tert-butyl 3-(bromomethyl)-6-fluoro-1H-indazole-1-carboxylate

HRID 343141Notes

Reaction equation

HRID 343141 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([F:17])[CH:15]=2)[C:10]([CH3:18])=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:19]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:19][CH2:18][C:10]1[C:11]2[C:16](=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[N:9]=1

Participants

5

Reactant 3

HCID 7187Benzoyl PeroxideHCID 67184N-bromobutanimideHCID 53779261tert-butyl 6-fluoro-3-methyl-1H-indazole-1-carboxylate

Product 1

HCID 10568325Tert-butyl 3-(bromomethyl)-6-fluoro-1H-indazole-1-carboxylateYield 60.9%

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Procedure

12.68 g (50.7 mmol) 6-Fluoro-3-methyl-indazole-1-carboxylic acid tert-butyl ester, prepared as in Part C, is combined with 9.92 g (55.7 mmol, 1.1 equiv) N-Bromosuccinimide and 1.23 g (5.1 mmol, 0.1 equiv) Benzoyl peroxide in 600 mL CCl4 and refluxed 10 h. The reaction mixture is filtered and the filtrate concentrated in vacuo and purified by flash chromatography on 300 g silica gel eluted successively with DCM/Hexanes (1:2, 3 L), (1:1, 3 L). Appropriate fractions were combined and concentrated in vacuo to give 10.18 g (30.9 mmol) of 3-Bromomethyl-6-fluoro-1-tert-butoxycarbonyl-1H-indazole as an amber oil: 1H NMR (CDCl3, 300 MHz) δ7.82 (m, 2H), 7.13 (m, 1H), 4.76 (s, 2H), 1.72 (s, 9H); TLC Rf =0.17 (EtOAc/Hexanes, 1:19).

Workup

  1. temperaturerefluxed 10 h
  2. filtrationThe reaction mixture is filtered
  3. concentrationthe filtrate concentrated in vacuo
  4. custompurified by flash chromatography on 300 g silica gel
  5. washeluted successively with DCM/Hexanes (1:2, 3 L), (1:1, 3 L)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8ceaa4b03f984f8a8e165baaf3bc9ecc
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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