Boron tribromide → N-[(3-fluorophenyl)-methyl]-2-(2-hydroxy-ethoxy)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid amide

HRID 242122Notes

Reaction equation

HRID 242122 reaction equation
B(Br)(Br)Br.[F:5][C:6]1[CH:7]=[C:8]([CH2:12][NH:13][C:14]([C:16]2[C:17]([O:31][CH2:32][CH2:33][O:34]C)=[N:18][C:19]3[C:24]([C:25]=2[CH3:26])=[CH:23][CH:22]=[C:21]([C:27]([F:30])([F:29])[F:28])[CH:20]=3)=[O:15])[CH:9]=[CH:10][CH:11]=1>C(Cl)Cl>[F:5][C:6]1[CH:7]=[C:8]([CH2:12][NH:13][C:14]([C:16]2[C:17]([O:31][CH2:32][CH2:33][OH:34])=[N:18][C:19]3[C:24]([C:25]=2[CH3:26])=[CH:23][CH:22]=[C:21]([C:27]([F:29])([F:30])[F:28])[CH:20]=3)=[O:15])[CH:9]=[CH:10][CH:11]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 56848231N-[(3-fluorophenyl)-methyl]-2-(2-methoxy-ethoxy)-4-methyl-7-(trifluoro-methyl)-quinoline-3-carboxylic acid amide

Product 1

HCID 56848233N-[(3-fluorophenyl)-methyl]-2-(2-hydroxy-ethoxy)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid amideYield 33.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

9.2 ml (9.2 mmol, 1M in DCM) boron tribromide was added in drops at −50° C. to a solution of 399 mg (0.9 mmol) N-[(3-fluorophenyl)-methyl]-2-(2-methoxy-ethoxy)-4-methyl-7-(trifluoro-methyl)-quinoline-3-carboxylic acid amide (Example 7) in DCM (8 ml). The mixture was subsequently heated to 0° C. within 2 h and stirred for 1 h at 0° C. The mixture was then stirred for 1 h at 10° C. It was thereafter quenched with a 0.5 M aq. NaHCO3 sol. and diluted with MeOH and DCM. The organic phase was separated and washed with a 10%-strength aq. Na2S2O3 sol., dried over MgSO4 and concentrated in a vacuum. After crystallisation (EtOAc/hexane 1:1) of the residue, 109 mg (0.3 mmol, 29%) N-[(3-fluorophenyl)-methyl]-2-(2-hydroxy-ethoxy)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid amide (example 9) was obtained. MS: m/z 423.1 [M+H]+.

Workup

  1. stirringThe mixture was then stirred for 1 h at 10° C
  2. customIt was thereafter quenched with a 0.5 M aq. NaHCO3 sol.
  3. additiondiluted with MeOH and DCM
  4. customThe organic phase was separated
  5. washwashed with a 10%-strength aq. Na2S2O3 sol.
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in a vacuum
  8. customAfter crystallisation (EtOAc/hexane 1:1) of the residue

Sources & evidence

ORD record
ord-655f2aeff3cf4ccdb41839f4ba23299b
Source dataset
uspto-grants-2014_02
Patent number
US08653101B2

Reaction notes

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