Triethylamine → 1h-Indazole-1-carboxylic acid,5-(chloromethyl)-3-(3-fluorophenyl)-,1,1-dimethylethyl ester

HRID 1983458Notes

Reaction equation

HRID 1983458 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([CH2:17]O)[CH:15]=3)[N:10]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.CS([Cl:37])(=O)=O.C(OCC)(=O)C>C(Cl)Cl>[Cl:37][CH2:17][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[N:9]=[C:8]2[C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 31297Methanesulfonyl chlorideHCID 222608021h-Indazole-1-carboxylic acid,3-(3-fluorophenyl)-5-(hydroxymethyl)-,1,1-dimethylethyl ester

Product 1

HCID 222606161h-Indazole-1-carboxylic acid,5-(chloromethyl)-3-(3-fluorophenyl)-,1,1-dimethylethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under ice-cooling, to a solution of 3.0 g of tert-butyl 3-(3-fluorophenyl)-5-(hydroxymethyl)-1H-1-indazolecarboxylate in 30 ml methylene chloride were added 1.6 ml of triethylamine and 0.78 ml of methanesulfonyl chloride, and the mixture was stirred at room temperature for one day. To the reaction mixture was added 180 ml of ethyl acetate, and the mixture was sequentially washed with water, 1 N hydrochloric acid, water, saturated aqueous sodium hydrogencarbonate solution and brine, dried over anhydrous magnesium sulfate and the solvent was evaporated. The crude product was purified and separated by silica gel column chromatography (toluene), to give 2.74 g of the title compound as yellow crystals.

Workup

  1. washthe mixture was sequentially washed with water, 1 N hydrochloric acid, water, saturated aqueous sodium hydrogencarbonate solution and brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. customthe solvent was evaporated
  4. customThe crude product was purified
  5. customseparated by silica gel column chromatography (toluene)

Sources & evidence

ORD record
ord-be19ed026f154d6dbb5ed73a60598c7b
Source dataset
uspto-grants-2009_06
Patent number
US07541376B2

Reaction notes

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