Citric Acid → HCID 22050793, compound

HRID 1867146Notes

Reaction equation

HRID 1867146 reaction equation
Br[CH2:2][C:3]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:4]=1[C:5]#[N:6].[OH:12][C:13]1[CH:18]=[C:17]([CH3:19])[N:16]([C:20]2[CH:21]=[C:22]([CH:27]=[CH:28][C:29]=2[CH3:30])[C:23]([O:25][CH3:26])=[O:24])[C:15](=[O:31])[CH:14]=1.C([O-])([O-])=O.[K+].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[C:5]([C:4]1[CH:7]=[C:8]([F:11])[CH:9]=[CH:10][C:3]=1[CH2:2][O:12][C:13]1[CH:18]=[C:17]([CH3:19])[N:16]([C:20]2[CH:21]=[C:22]([CH:27]=[CH:28][C:29]=2[CH3:30])[C:23]([O:25][CH3:26])=[O:24])[C:15](=[O:31])[CH:14]=1)#[N:6]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 11430Potassium Carbonate2×HCID 220157702-(Bromomethyl)-5-fluorobenzonitrile2×HCID 54724193methyl 3-(4-hydroxy-6-methyl-2-oxopyridin-1(2H)-yl)-4-methylbenzoate

Product 1

HCID 22050793HCID 22050793, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cooled (0° C.) solution of 2-(bromomethyl)-5-fluorobenzonitrile (4.31 g, 20.1 mmol) and methyl 3-(4-hydroxy-6-methyl-2-oxopyridin-1(2H)-yl)-4-methylbenzoate (5.00 g, 18.3 mmol) in DMF (20 mL) was added K2CO3 (3.00 g, 22.0 mmol). The reaction was allowed to warm to RT and stirred overnight. Additional 2-(bromomethyl)-5-fluorobenzonitrile (0.39 g, 1.83 mmol) and K2CO3 (0.25 g, 1.83 mmol) were added and the reaction heated at 60° C. for 2 h. Solvent removed by distillation. Reaction neutralized with 5% citric acid (50 mL). Organic products were extracted in DCM (3×25 mL), dried over Na2SO4, filtered, and concentrated to a thick dark brown oil. Purified by silica gel flash column chromatography using EtOAc as the eluent to give the product as a brown solid, dried in vacuo (6.18 g, 76%). 1H NMR (CD3OD/400 MHz) δ8.03 (m, 1H), 7.76 (m, 2H), 7.66 (m, 1H), 7.52 (m, 2H), 6.24 (s, 1H), 6.09 (s, 1H), 5.27 (s, 2H), 3.89 (s, 3H), 2.12 (s, 3H), 1.90 (s, 3H). ESHRMS m/z 407.1408 (M+H calculated for C23H20FN2O4 requires 407.1402).

Workup

  1. temperaturethe reaction heated at 60° C. for 2 h
  2. customSolvent removed by distillation
  3. customReaction
  4. extractionOrganic products were extracted in DCM (3×25 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to a thick dark brown oil
  8. customPurified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-302b033a3dc740ffa0b8fb2a6b30e189
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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