Water → HCID 22050979, compound

HRID 1867065Notes

Reaction equation

HRID 1867065 reaction equation
[OH:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]([C:9]2[CH:14]=[C:13]([CH2:15][OH:16])[CH:12]=[CH:11][C:10]=2[CH3:17])[C:4](=[O:18])[CH:3]=1.[F:19][C:20]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:21]=1[CH2:22]Br.C([O-])([O-])=O.[K+].[K+].O>CN(C)C=O.C(#N)C.O>[F:19][C:20]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:21]=1[CH2:22][O:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]([C:9]2[CH:14]=[C:13]([CH2:15][OH:16])[CH:12]=[CH:11][C:10]=2[CH3:17])[C:4](=[O:18])[CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 54724207HCID 54724207, compound

Product 1

HCID 22050979HCID 22050979, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

4-hydroxy-1-[5-(hydroxymethyl)-2-methylphenyl]-6-methyl pyridin-2(1H)-one (from Step 1) (8.0 g, 32.6 mmol) was stirred briskly at room temperature with 2,4-difluorobenzyl bromide (4.2 ml, 32.6 mmol) and K2CO3 (4.5 g, 32.6 mmol) in 50 ml of dimethylformamide. After stirring for 8 hours, H2O (100 ml) was added to reaction mixture. The product was extracted with ethyl acetate. Ethyl acetate layer was separated and dried over Na2SO4. Ethyl acetate was removed in vacuo. A yellow oil was obtained. The oil was passed through a plug of silica gel first eluting with 500 ml of ethyl acetate/hexane (1:1) This eluent was set aside. Next, ethyl acetate (100%) was passed through the plug until desired product was completely flushed from silica (3 liters). Solvent was removed in vacuo. Light yellow oil obtained (7.5 g, 62%). 1H NMR (300 MHz, CD3OD) δ 7.60 (app q, J=6.44 Hz, 1H), 7.42 (d, J=0.81 Hz, 2H), 7.15 (s, 1H) 7.06 (m, 2H), 6.21 (dd, J=1.61, 1.00 Hz, 1H), 6.12 (d, J=2.62 Hz, 1H), 5.16 (s, 2H), 4.65 (s, 2H), 2.07 (s, 3H), 1.93 (s, 3H); LC/MS, tr=2.38 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 372 (M+H).

Workup

  1. extractionThe product was extracted with ethyl acetate
  2. customEthyl acetate layer was separated
  3. dry with materialdried over Na2SO4
  4. customEthyl acetate was removed in vacuo
  5. customA yellow oil was obtained
  6. washeluting with 500 ml of ethyl acetate/hexane (1:1) This eluent
  7. customwas completely flushed from silica (3 liters)
  8. customSolvent was removed in vacuo
  9. customLight yellow oil obtained (7.5 g, 62%)

Sources & evidence

ORD record
ord-8165982f716043dbbda606339000ea75
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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