Benzoyl Peroxide → 3-(Bromomethyl)-1H-indazole, N1-BOC protected

HRID 343113Notes

Reaction equation

HRID 343113 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH3:17])=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:18]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:18][CH2:17][C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[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 10775939tert-Butyl 3-methyl-1H-indazole-1-carboxylate

Product 1

HCID 108049513-(Bromomethyl)-1H-indazole, N1-BOC protected

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Procedure

A stirring solution of 53.4 g (0.23 mol) of 1-tert-butoxycarbonyl-3-methylindazole, prepared as in Part B, in 1.0 L of CCl4 is heated to reflux, and then a mixture of 45.1 g (0.25 mol, 1.1 equiv) of N-bromosuccinimide and 5.7 g (23.5 mmol, 0.1 equiv) of benzoyl peroxide is added portionwise over 5 min as a solid. The resulting solution is heated at reflux for 4.5 h, then cooled to RT. The reaction mixture is filtered through a pad of Celite to remove the precipitated succinimide, and the solvent is removed in vacuo. Purification of the crude material by gradient silica gel flash column chromatography using hexane/EtOAc 15/1 to hexane/EtOAc 3/1 as eluent afforded 43.2 of the title compound as a white solid: 1H NMR (CDCl3, 300 MHz) δ8.20 (d, 1H, J=7.8), 7.88 (d, 1H, J=7.8), 7.60 (dd, 1H, J=7.3, 7.3), 7.41 (dd, 1H, J=7.3, 7.3), 4.91 (s, 2H), 1.77 (s, 9H); ;TLC Rf =0.56 (EtOAc/Hexane 1/5).

Workup

  1. temperatureto reflux
  2. additionis added portionwise over 5 min as a solid
  3. temperatureThe resulting solution is heated
  4. temperatureat reflux for 4.5 h
  5. filtrationThe reaction mixture is filtered through a pad of Celite
  6. customto remove the precipitated succinimide
  7. customthe solvent is removed in vacuo
  8. customPurification of the crude material by gradient silica gel flash column chromatography

Sources & evidence

ORD record
ord-1be2a77c7b4c4d0bbff8762b027ac01b
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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