4-Fluorobenzylamine → 2-Bromo-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamide

HRID 1879154Notes

Reaction equation

HRID 1879154 reaction equation
[Br:1][C:2]1[S:3][C:4]([C:8]([OH:10])=O)=[C:5]([CH3:7])[N:6]=1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[F:47][C:48]1[CH:55]=[CH:54][C:51]([CH2:52][NH2:53])=[CH:50][CH:49]=1>ClCCl>[F:47][C:48]1[CH:55]=[CH:54][C:51]([CH2:52][NH:53][C:8]([C:4]2[S:3][C:2]([Br:1])=[N:6][C:5]=2[CH3:7])=[O:10])=[CH:50][CH:49]=1

Participants

6

Reactant 4

HCID 673264-FluorobenzylamineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 28240582-Bromo-4-methyl-1,3-thiazole-5-carboxylic acid

Product 1

HCID 666314052-Bromo-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamideYield 57.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Part A. To a solution of 2-bromo-4-methyl-thiazole-5-carboxylic acid (10 g, 45.0 mmol, 1.0 equiv) and diisopropylethylamine (15.6 mL, 90.0 mmol, 2.0 equiv) in anhydrous dichloromethane (400 mL) was added benzotriazol-1-yloxytris-(dimethylamino)phosphonium hexafluorophosphate (BOP reagent, 22 g, 49.5 mmol, 1.1 equiv) and 4-fluorobenzylamine (5.7 mL, 49.5 mmol, 1.1 equiv). The resulting mixture was stirred at ambient temperature for 12 hr. The reaction mixture was diluted with dichloromethane, washed with water then brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by column chromatography [SiO2, ethyl acetate/hexanes, 10:90 to 40:60, v/v], followed by stirring in pentane and filtering the solid to afford 2-bromo-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamide (8.5 g, 57% yield). MS (M+H)+=330.1, Rt=1.36 min.

Workup

  1. washwashed with water
  2. dry with materialbrine, dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by column chromatography [SiO2, ethyl acetate/hexanes, 10:90 to 40:60
  6. stirringby stirring in pentane
  7. filtrationfiltering the solid

Sources & evidence

ORD record
ord-a1dbc3f855a0427ca98942917811b967
Source dataset
uspto-grants-2012_11
Patent number
US08314138B2

Reaction notes

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