Hydrogen Peroxide → (5-{2-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-4-trifluoromethyl-phenyl}-6-methoxy-pyridin-3-yl)-acetic acid

HRID 554618Notes

Reaction equation

HRID 554618 reaction equation
[CH2:1]([N:3]([CH2:9][C:10]1[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=1[C:20]1[C:21]([O:32][CH3:33])=[N:22]C=C(C#C[Si](C)(C)C)[CH:25]=1)C(C1CC1)=O)[CH3:2].[O:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1.B.[OH:40]O.[OH-].[Na+].[CH2:44]1[CH2:48][O:47][CH2:46][CH2:45]1>CO>[CH:37]1([C:38]([N:3]([CH2:9][C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=2[C:20]2[CH:25]=[C:44]([CH2:45][C:46]([OH:40])=[O:47])[CH:48]=[N:22][C:21]=2[O:32][CH3:33])[CH2:1][CH3:2])=[O:34])[CH2:35][CH2:36]1

Participants

7

Reactant 5

HCID 784Hydrogen Peroxide2×HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 67212431Cyclopropanecarboxylic acid ethyl-[2-(2-methoxy-5-trimethylsilanylethynyl-pyridin-3-yl)-5-trifluoromethyl-benzyl]-amide

Product 1

HCID 45138482(5-{2-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-4-trifluoromethyl-phenyl}-6-methoxy-pyridin-3-yl)-acetic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To cyclopropanecarboxylic acid ethyl-[2-(2-methoxy-5-trimethylsilanylethynyl-pyridin-3-yl)-5-trifluoromethyl-benzyl]-amide (0.205 g, 0.42 mmol) in THF (2 mL) at 0° C. was added borane tetrahydrofuran complex (1M in THF; 0.48 mL, 0.48 mmol), and the reaction was stirred for 2 hours. Once no starting material was seen by analytical LCMS, MeOH (0.22 mL), hydrogen peroxide (0.04 mL, 0.43 mmol), and 3M aqueous sodium hydroxide (0.22 ml) was added, and the reaction was stirred for 1 hour. Additional hydrogen peroxide (0.1 mL) was added, and the reaction was stirred for another hour. The mixture was then acidified and extracted with EtOAc, and the combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by preparative HPLC to give Compound 10.

Workup

  1. additionwas added
  2. stirringthe reaction was stirred for 1 hour
  3. stirringthe reaction was stirred for another hour
  4. extractionextracted with EtOAc
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-1f32a24ebee64fc39a0f621e98e9a093
Source dataset
uspto-grants-2011_11
Patent number
US08049015B2

Reaction notes

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