Allyl bromide → Ethyl 6-(allyloxy)-5-(benzyloxy)-2-(methylthio)pyrimidine-4-carboxylate

HRID 1093115Notes

Reaction equation

HRID 1093115 reaction equation
[CH3:1][S:2][C:3]1[NH:4][C:5](=[O:22])[C:6]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:7]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[N:8]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:30][CH:31]=[CH2:32]>CN(C=O)C>[CH2:32]([O:22][C:5]1[N:4]=[C:3]([S:2][CH3:1])[N:8]=[C:7]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:6]=1[O:14][CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[CH:31]=[CH2:30]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 10796Cesium carbonateHCID 135772690Ethyl 5-(benzyloxy)-2-(methylthio)-6-oxo-1,6-dihydropyrimidine-4-carboxylate

Product 1

HCID 57904914Ethyl 6-(allyloxy)-5-(benzyloxy)-2-(methylthio)pyrimidine-4-carboxylateYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-methylsulfanyl-1,6-dihydro-6-oxo-5-(phenylmethoxy)-4-pyrimidinecarboxylic acid, ethyl ester (4.28 g, 13.36 mmol) in DMF (70 mL) was added Cs2CO3 (4.35 g, 13.36 mmol) followed by 3-bromoprop-1-ene (1.156 mL, 13.36 mmol). The resulting mixture was stirred at 80° C. for 1 h, cooled to room temperature and partitioned between ethyl acetate and hexane. The organic phase was washed with water followed by brine, dried (Na2SO4) and filtered. Concentration gave an oil that was purified by flash column chromatography (Biotage flash chromatography system, 0%-40% ethyl acetate/hexane, 16 CV) to give the title compound as a yellow oil (1.8144 g, 38% yield). 1H NMR (300 MHz, CDCl3) δ: 7.41-7.37 (2H, m), 7.36-7.28 (3H, m), 6.10-5.97 (1H, m), 5.40 (2H, dq, J=17.2, 1.5 Hz), 5.29 (2H, dq, J=10.5, 1.2 Hz), 5.03 (2H, s), 4.93 (2H, dt, J=5.6, 1.4 Hz), 4.32 (2H, q, J=7.1 Hz), 4.32 (2H, q, J=7.1 Hz), 2.50 (2H, q, J=7.1 Hz), 1.28 (3H, t, J=7.1 Hz). LCMS (M+H) calcd for C18H21N2O4S: 361.12; found: 361.21.

Workup

  1. temperaturecooled to room temperature
  2. custompartitioned between ethyl acetate and hexane
  3. washThe organic phase was washed with water
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationConcentration
  7. customgave an oil that
  8. customwas purified by flash column chromatography (Biotage flash chromatography system, 0%-40% ethyl acetate/hexane, 16 CV)

Sources & evidence

ORD record
ord-6d65a9ef0b5d4e21bef27718a1803704
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

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