Reaction #68355

ord-a6f2a3e9edb642ceb8a3affd420e4f14

Reaction equation

CC(C)c1c(C(=O)NCc2ccc(F)c(F)c2)c2ccc(CO)cc2n1Cc1ccccc1
1-benzyl-N-(3,4-difluorobenzyl)-6-(hydroxymethyl)-2-isopropyl-1H-indole-3-carboxamide
CC(C)c1c(C(=O)NCc2ccc(F)c(F)c2)c2ccc(CO)cc2n1Cc1ccccc1
Compound 52
CC(C)c1c(C(=O)NCc2ccc(F)c(F)c2)c2ccc(CO)cc2n1Cc1ccccc1
1-benzyl-N-(3,4-difluorobenzyl)-6-(hydroxymethyl)-2-isopropyl-1H-indole-3-carboxamide
C[N+]1([O-])CCOCC1
NMO
→
CC(C)c1c(C(=O)NCc2ccc(F)c(F)c2)c2ccc(C=O)cc2n1Cc1ccccc1
title compound
CC(C)c1c(C(=O)NCc2ccc(F)c(F)c2)c2ccc(C=O)cc2n1Cc1ccccc1
1-Benzyl-N-(3,4-difluorobenzyl)-6-formyl-2-isopropyl-1H-indole-3-carboxamide

Reactants

—
powder
CC(C)c1c(C(=O)NCc2ccc(F)c(F)c2)c2ccc(CO)cc2n1Cc1ccccc1
1-benzyl-N-(3,4-difluorobenzyl)-6-(hydroxymethyl)-2-isopropyl-1H-indole-3-carboxamide
CC(C)c1c(C(=O)NCc2ccc(F)c(F)c2)c2ccc(CO)cc2n1Cc1ccccc1
Compound 52
CC(C)c1c(C(=O)NCc2ccc(F)c(F)c2)c2ccc(CO)cc2n1Cc1ccccc1
1-benzyl-N-(3,4-difluorobenzyl)-6-(hydroxymethyl)-2-isopropyl-1H-indole-3-carboxamide
C[N+]1([O-])CCOCC1
NMO

Reagents

CCC[N+](CCC)(CCC)CCC.[O]=[Ru](=[O])(=[O])[O-]
TPAP

Solvents

ClCCl
CH2Cl2

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    Concentrationconcentrated in vacuo
  2. 2
    OtherThe residue was purified by chromatography on silica gel (0→25% EtOAc-hexanes)

Procedure

To a solution of 1-benzyl-N-(3,4-difluorobenzyl)-6-(hydroxymethyl)-2-isopropyl-1H-indole-3-carboxamide (Compound 52, 340 mg, 0.759 mmol) in CH2Cl2 (10 ml) at 25° C. under argon was added molecular sieve powder (300 mg), NMO (267 mg, 2.28 mmol), TPAP (26 mg, 0.08 mmol). The reaction was stirred for 10 minutes, then concentrated in vacuo. The residue was purified by chromatography on silica gel (0→25% EtOAc-hexanes) to yield the title compound as a light yellow solid.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08524917B2uspto-grants-2013_09