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

HRID 1713201
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HRID 1713201 반응식
[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
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참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 2855718-Crown-6
촉매
HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-c0f3099f77cb4707a9af7c7d815b562c
출처 데이터셋
uspto-grants-2010_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07795271B2

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