Dimethylformamide → HCID 22050866, compound

HRID 1867089Notes

Reaction equation

HRID 1867089 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][OH:9])=[CH:4][C:3]=1[N:10]1[C:15]([CH3:16])=[CH:14][C:13]([OH:17])=[CH:12][C:11]1=[O:18].CN(C)C=O.C(=O)([O-])[O-].[K+].[K+].[F:30][C:31]1[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:32]=1[CH2:33]Br>C([O-])(O)=O.[Na+]>[F:30][C:31]1[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:32]=1[CH2:33][O:17][C:13]1[CH:14]=[C:15]([CH3:16])[N:10]([C:3]2[CH:4]=[C:5]([CH2:8][OH:9])[CH:6]=[CH:7][C:2]=2[F:1])[C:11](=[O:18])[CH:12]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 54724208HCID 54724208, compound

Product 1

HCID 22050866HCID 22050866, compound

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

A 100 mL roundbottomed flask (nitrogen purged) was charged with 1-[2-fluoro-5-(hydroxymethyl)phenyl]-4-hydroxy-6-methylpyridin-2(1H)-one (1.2 g, 4.82 mmol) and N,N-dimethyl formamide (10 mL). Potassium carbonate (0.6 g, 4.4 mmol) and 2,4-difluorobenzyl bromide (0.56 mL, 4.4 mmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with saturated aqueous NaHCO3 and extracted with ethyl acetate. The organic layer was concentrated in vacuo and the residue was chromatographed on silica (9:1 methylene chloride: ethanol). The impure oil (0.3 g, 17%) was carried on without further purification. 1H NMR (400 MHz, CD3OD) δ 7.54 (m, 2H), 7.30 (m, 2H), 7.02 (m, 2H), 6.17 (dd, J=1 and 2.8 Hz, 1H), 6.03 (d, j=2.8 Hz, 1H), 5.14 (s, 2H), 4.62 (s, 2H), 2.14 (s, 3H) ppm. 19F NMR (400 MHz, CD3OD) δ −111.35 (1F), −115.97 (1F), −127.31 (1F) ppm. LC/MS, tr=5.05 minutes (5 to 95% acetonitrile/water over 8 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 375 (M+H).

Workup

  1. custom(nitrogen purged)
  2. extractionextracted with ethyl acetate
  3. concentrationThe organic layer was concentrated in vacuo
  4. customthe residue was chromatographed on silica (9:1 methylene chloride: ethanol)
  5. customThe impure oil (0.3 g, 17%) was carried on without further purification
  6. customLC/MS, tr=5.05 minutes (5 to 95% acetonitrile/water over 8 minutes at 1 ml/min with detection 254 nm, at 50° C.)

Sources & evidence

ORD record
ord-e466877ff1d944eb889c59b247bc1943
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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