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Potassium Carbonate → methyl 4-{[4-[(2,4-difluorobenzyl)oxy]-2-methyl-6-oxopyrimidin-1(6H)-yl]methyl}benzoate

HRID 350899
Notes
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Reaction equation

HRID 350899 reaction equation
[OH:1][C:2]1[N:3]=[C:4]([CH3:20])[N:5]([CH2:9][C:10]2[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH:11]=2)[C:6](=[O:8])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[F:27][C:28]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:29]=1[CH2:30]Br>CN(C=O)C.C1OCCOCCOCCOCCOCCOC1>[F:27][C:28]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:29]=1[CH2:30][O:1][C:2]1[N:3]=[C:4]([CH3:20])[N:5]([CH2:9][C:10]2[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH:11]=2)[C:6](=[O:8])[CH:7]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 135737356methyl 4-[(4-hydroxy-2-methyl-6-oxopyrimidin-1(6H)-yl)methyl]benzoate

Product 1

HCID 21090204methyl 4-{[4-[(2,4-difluorobenzyl)oxy]-2-methyl-6-oxopyrimidin-1(6H)-yl]methyl}benzoateYield 69%

Reagents, catalysts & solvents 2

HCID 28557
18-Crown-6
Catalyst
HCID 6228DimethylformamideSolvent

Procedure

A mixture of methyl 4-[(4-hydroxy-2-methyl-6-oxopyrimidin-1(6H)-yl)methyl]benzoate (0.2 g, 0.00073 mol, from step 2), potassium carbonate (0.15 g, 0.001 mol), 2,4 difluorobenzylbromide (0.15 g, 0.00073 mol), and 18-crown-6 (0.011 g) in DMF is stirred at room temperature for 1 h under argon atmosphere. The DMF was distilled in vacuo and the residue is partitioned between dichloromethane (20 mL) and water (20 mL). The organic phase is washed with water, dried (Na2SO4), filtered and concentrated under reduced pressure. The resulting residue is purified by silica gel flash chromatography using 35% EtOAc in hexanes to afford the title compound (0.20 g, 69%) as a white powder: 1H NMR (CD3OD/400 MHz) δ 7.98 (d 2H, J=8.4 Hz), 7.54 (m, 1H), 7.27 (d, 2H, J=8.4 Hz), 6.98 (m, 2H), 5.78 (s, 1H), 5.38 (s, 2H), 5.32 (s, 2H), 3.88 (s, 3H), and 2.44 (s, 3H); ES-HRMS m/z 401.1308 (M+H calcd for C21H19N2O4F2 requires 401.1307). 19F NMR(CD3OD/400 MHz) −111.77 (m), 116.06 (m).

Workup

  1. distillationThe DMF was distilled in vacuo
  2. customthe residue is partitioned between dichloromethane (20 mL) and water (20 mL)
  3. washThe organic phase is washed with water
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue is purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-920d88ae4e2a42c8a88eb94d7fe748cc
Source dataset
uspto-grants-2007_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07183287B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes