Acetic Acid → 4-{[4-[(2,4-difluorobenzyl)oxy]-2-methyl-6-oxopyrimidin-1(6H)-yl]methyl}benzoic acid

HRID 350900Notes

Reaction equation

HRID 350900 reaction equation
[F:1][C:2]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:3]=1[CH2:4][O:5][C:6]1[N:7]=[C:8]([CH3:24])[N:9]([CH2:13][C:14]2[CH:23]=[CH:22][C:17]([C:18]([O:20]C)=[O:19])=[CH:16][CH:15]=2)[C:10](=[O:12])[CH:11]=1.[OH-].[Na+].C(O)(=O)C>O1CCOCC1.O>[F:1][C:2]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:3]=1[CH2:4][O:5][C:6]1[N:7]=[C:8]([CH3:24])[N:9]([CH2:13][C:14]2[CH:23]=[CH:22][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=2)[C:10](=[O:12])[CH:11]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 21090204methyl 4-{[4-[(2,4-difluorobenzyl)oxy]-2-methyl-6-oxopyrimidin-1(6H)-yl]methyl}benzoate

Product 1

HCID 210890154-{[4-[(2,4-difluorobenzyl)oxy]-2-methyl-6-oxopyrimidin-1(6H)-yl]methyl}benzoic acidYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of methyl 4-{[4-[(2,4-difluorobenzyl)oxy]-2-methyl-6-oxopyrimidin-1(6H)-yl]methyl}benzoate (0.20 g, 0.0005 mol, from step 3) and 2N NaOH (0.4 mL, 0.0008 mol) in dioxane (0.25 mL) is stirred at room temperature for 45 min. The resulting clear solution is diluted with water (5.0 mL), acidified with acetic acid and extracted with dichloromethane (2×10 mL). The combined organic extracts are washed with water (2×10 mL), dried (Na2SO4), filtered and concentrated to dryness to afford the title compound (0.15 g, 78%) as a white powder: 1H NMR (CD3OD/400 MHz) δ 7.99 (d, 2H, J=8.0 Hz), 7.54 (m, 1H,), 7.27 (d, 2H, J=8.0 Hz), 6.00 (m, 2H), 5.78 (s, 1H), 5.39 (s, 2H), 5.32 (s, 2H), 2.45 (s, 3H), and 2.13 (s, 3H); ES-HRMS m/z 387.1134 (M+H calcd for C20H17N2O4F2 requires 387.1151). 19F NMR(CD3OD/400 MHz) −111.79 (m) and −116.08 (m)

Workup

  1. extractionextracted with dichloromethane (2×10 mL)
  2. washThe combined organic extracts are washed with water (2×10 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-3e74657026534ddd95550fa6e0c3cee3
Source dataset
uspto-grants-2007_02
Patent number
US07183287B2

Reaction notes

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