N-(4,5-Difluoro-2-(hydroxymethyl)phenyl)pivalamide → N-(4,5-Difluoro-2-formylphenyl)pivalamide

HRID 2378668Notes

Reaction equation

HRID 2378668 reaction equation
[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.[F:12][C:13]1[C:18]([F:19])=[CH:17][C:16]([NH:20][C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])=[C:15]([CH2:27][OH:28])[CH:14]=1>C(Cl)Cl>[F:12][C:13]1[C:18]([F:19])=[CH:17][C:16]([NH:20][C:21](=[O:26])[C:22]([CH3:23])([CH3:24])[CH3:25])=[C:15]([CH:27]=[O:28])[CH:14]=1

Participants

4

Reactant 2

HCID 59732039N-(4,5-Difluoro-2-(hydroxymethyl)phenyl)pivalamideHCID 178418287HCID 178418287, compound

Product 1

HCID 59732008N-(4,5-Difluoro-2-formylphenyl)pivalamideYield 26%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Pyridiniumchlorochromate (9.36 g, 43.4 mmol) was added to the solution of the crude N-(4,5-difluoro-2-(hydroxymethyl)phenyl)pivalamide in CH2Cl2 (150 mL) at rt. The yellow solution turned into dark brown in 10 min, and the mixture was continued stirring for 3 hr, and then passed through a thin silica gel pad with CH2Cl2 (2×50 mL). The combined organic solution was concentrated on rotary vacuum, and purified on flash chromatography eluting with 20˜60% EtOAc/hexanes(1300 mL) to afford the expected product as a brown solid(1.91 g, 26% yield after three step); 1H NMR (400 MHz, CDCl3) δppm 1.29 (s, 9H), 7.42-7.48 (m, 1H), 8.75 (dd, J=13.35, 7.30 Hz, 1H), 9.77-9.80 (m, 1H), 11.40 (s, 1H); Mass spec. 242.08 (MH+), Calc. for C12H13F2NO2 241.09.

Workup

  1. customdark brown in 10 min
  2. concentrationThe combined organic solution was concentrated on rotary vacuum
  3. custompurified on flash chromatography
  4. washeluting with 20˜60% EtOAc/hexanes(1300 mL)

Sources & evidence

ORD record
ord-6c7646df7d30473cbcd6483f20f68f74
Source dataset
uspto-grants-2008_12
Patent number
US07470679B2

Reaction notes

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