Potassium Carbonate → HCID 11441746, compound

HRID 1831954Notes

Reaction equation

HRID 1831954 reaction equation
[Br:1][C:2]1[C:3](=[O:19])[NH:4][C:5](C)=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13](F)=[CH:12][C:11]=1F.Br[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([CH2:28][C:29]([OH:31])=[O:30])=[CH:24][CH:23]=1.C([O-])([O-])=O.[K+].[K+]>CN(C)C=O>[CH2:9]([O:8][C:7]1[CH:6]=[CH:5][N:4]([CH2:21][C:22]2[CH:23]=[CH:24][C:25]([CH2:28][C:29]([OH:31])=[O:30])=[CH:26][CH:27]=2)[C:3](=[O:19])[C:2]=1[Br:1])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 45190564-(Bromomethyl)phenylacetic acidHCID 220504293-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one

Product 1

HCID 11441746HCID 11441746, compoundYield 3.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one(0.5 g, 1.78 mmol) was dissolved in N,N-dimethylformamide (5 mL). 4-(Bromomethyl)phenylacetic acid (0.5 g, 2.14 mmol) was added followed by K2CO3 (0.3 g, 2.14 mmol). The reaction was heated to 80° C. and shaken for 16 hours, then heated to 100° C. and shaken for 16 hours more. The reaction mixture was partitioned between water and ethyl acetate and extracted with ethyl acetate (2×50 mL). The aqueous layer was acidified (pH 2) with 1N HCl and extracted with ethyl acetate (3×50 ml). The organic extracts were combined, washed with brine, dried over Na2SO4, and filtered. The filtrate was concentrated to an oil, and purified by chromatography (silica gel, hexane/ethyl acetate) followed by reversed phase chromatography (C18, 0.1% aqueous trifluoroacetic acid /acetonitrile) to yield a white solid (25 mg, 3%). 1H NMR (400 MHz, CDCl3) δ 7.40-7.38 (m, 3H), 7.25-7.20 (m, 7H), 6.05 (d, J=8.0 Hz, 1H), 5.21 (s, 2H); 5.13, (s, 2H); 3.62, (s, 2H). ES HRMS m/z 428.0510 (M+H C21H18BrNO4 requires 428.0492).

Workup

  1. temperatureheated to 100° C.
  2. stirringshaken for 16 hours more
  3. customThe reaction mixture was partitioned between water and ethyl acetate
  4. extractionextracted with ethyl acetate (2×50 mL)
  5. extractionextracted with ethyl acetate (3×50 ml)
  6. washwashed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated to an oil
  10. custompurified by chromatography (silica gel, hexane/ethyl acetate)

Sources & evidence

ORD record
ord-995fabc0c34f48878f6d05a116d0d361
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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