Potassium Carbonate → 6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl 1,1,2,2,2-pentafluoroethanesulfonate

HRID 1774051Notes

Reaction equation

HRID 1774051 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([N:24]2[CH:29]=[CH:28][C:27](=[O:30])[NH:26][C:25]2=[O:31])[CH:8]=[C:9]([C:13]2[CH:22]=[CH:21][C:20]3[C:15](=[CH:16][CH:17]=[C:18]([OH:23])[CH:19]=3)[CH:14]=2)[C:10]=1[O:11][CH3:12])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[F:38][C:39]([F:48])([S:44](F)(=[O:46])=[O:45])[C:40]([F:43])([F:42])[F:41]>CN(C)C=O>[F:38][C:39]([F:48])([S:44]([O:23][C:18]1[CH:17]=[CH:16][C:15]2[C:20](=[CH:21][CH:22]=[C:13]([C:9]3[CH:8]=[C:7]([N:24]4[CH:29]=[CH:28][C:27](=[O:30])[NH:26][C:25]4=[O:31])[CH:6]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[C:10]=3[O:11][CH3:12])[CH:14]=2)[CH:19]=1)(=[O:46])=[O:45])[C:40]([F:43])([F:42])[F:41]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 6451567Ethanesulfonyl fluoride, 1,1,2,2,2-pentafluoro-HCID 566406701-(3-tert-butyl-5-(6-hydroxynaphthalen-2-yl)-4-methoxyphenyl)pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 866939066-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl 1,1,2,2,2-pentafluoroethanesulfonate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of 10.0 g of 1-(3-tert-butyl-5-(6-hydroxynaphthalen-2-yl)-4-methoxyphenyl)pyrimidine-2,4(1H,3H)-dione (23.5 mmol, 1.0 equivalent) in 100 mL of N,N-dimethylformamide was added 6.5 g of 325-mesh potassium carbonate (47 mmol, 2.0 equivalents). 1,1,2,2,2-pentafluoroethanesulfonyl fluoride (4 g, 20 mmol, 0.85 equivalents) was bubbled sub-surface into the reaction mixture over 3 hours, and the mixture was stirred for 0.5 hours. The inorganic solids were separated by filtration, and the flask and filter cake were rinsed with 5 mL of N,N-dimethylformamide. The solution was diluted with 24 mL of water and 150 mL of ethyl acetate and the resultant solution was washed four times with 50 mL portions of 10 wt % aqueous sodium chloride, followed by 25 mL of saturated aqueous sodium chloride solution. The organic solution was dried over sodium sulfate, the drying agent was filtered off and the organic solution was concentrated in vacuo. The resultant solid was purified by chromatography over silica gel with gradient elution (40% ethyl acetate/hexanes to 60% ethyl acetate/hexanes). The desired product was dissolved in 10 mL of ethyl acetate and 200 mL of heptanes was added over 60 minutes. The product crystallized and was isolated by filtration. The wet cake was washed with 40 mL of heptanes and dried in vacuo with heating at 50° C. The title compound was isolated as a white solid (9.4 g, 67% yield). 1H NMR (600 MHz, CDCl3) δ ppm 8.60 (d, J=0.5 Hz, 1H), 8.06 (d, J=0.8 Hz, 1H), 7.97 (d, J=9.1 Hz, 1H), 7.94 (d, J=8.7 Hz, 1H), 7.84 (dd, J=8.5, 1.7 Hz, 1H), 7.80 (d; J=2.5 Hz, 1H), 7.42 (dd, J=9.0, 2.5 Hz, 1H), 7.37 (d, J=8.0 Hz, 1H), 7.27-7.26 (m, 2H), 5.82 (dd, J=8.0, 2.3 Hz, 1H), 3.30 (s, 3H), 1.46 (s, 9H). 13C NMR (101 MHz, CDCl3) δ ppm 162.6 (C), 157.5 (C), 149.8 (C), 147.1 (C), 145.0 (C), 144.5 (CH), 137.2 (C), 135.1 (C), 133.0 (C), 132.23 (C), 132.18 (C), 130.5 (CH), 128.5 (CH), 128.1 (CH), 127.4 (CH), 127.2 (CH), 124.4 (CH), 119.9 (CH), 118.9 (CH), 102.4 (CH), 61.0 (CH3), 35.8 (C), 30.8 (CH3). 19F NMR (564 MHz, CDCl3) δ ppm −79.1 (3F), −113.4 (2F). LC-MS m/z 599.1 [M+H]+.

Workup

  1. customThe inorganic solids were separated by filtration
  2. filtrationthe flask and filter cake
  3. washwere rinsed with 5 mL of N,N-dimethylformamide
  4. additionThe solution was diluted with 24 mL of water and 150 mL of ethyl acetate
  5. washthe resultant solution was washed four times with 50 mL portions of 10 wt % aqueous sodium chloride
  6. dry with materialThe organic solution was dried over sodium sulfate
  7. filtrationthe drying agent was filtered off
  8. concentrationthe organic solution was concentrated in vacuo
  9. customThe resultant solid was purified by chromatography over silica gel with gradient elution (40% ethyl acetate/hexanes to 60% ethyl acetate/hexanes)
  10. dissolutionThe desired product was dissolved in 10 mL of ethyl acetate
  11. addition200 mL of heptanes was added over 60 minutes
  12. customThe product crystallized
  13. customwas isolated by filtration
  14. washThe wet cake was washed with 40 mL of heptanes
  15. customdried in vacuo

Sources & evidence

ORD record
ord-b7e7e7adb24d4aafa19fff2cffa024d0
Source dataset
uspto-grants-2016_02
Patent number
US09255074B2

Reaction notes

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