N-bromobutanimide → 4-Bromomethyl-3-(2,4-dimethoxy-pyrimidin-5-yl)-7-methoxy-chromen-2-one

HRID 747872Notes

Reaction equation

HRID 747872 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[C:7]([O:9][CH3:10])[C:6]([C:11]2[C:12](=[O:24])[O:13][C:14]3[C:19]([C:20]=2[CH3:21])=[CH:18][CH:17]=[C:16]([O:22][CH3:23])[CH:15]=3)=[CH:5][N:4]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C1C(=O)N([Br:42])C(=O)C1>C1COCC1>[Br:42][CH2:21][C:20]1[C:19]2[C:14](=[CH:15][C:16]([O:22][CH3:23])=[CH:17][CH:18]=2)[O:13][C:12](=[O:24])[C:11]=1[C:6]1[C:7]([O:9][CH3:10])=[N:8][C:3]([O:2][CH3:1])=[N:4][CH:5]=1

Participants

5

Reactant 3

HCID 67184N-bromobutanimideHCID 2733832Lithium HexamethyldisilazideHCID 116742933-(2,4-Dimethoxy-pyrimidin-5-yl)-7-methoxy-4-methyl-chromen-2-one

Product 1

HCID 115822324-Bromomethyl-3-(2,4-dimethoxy-pyrimidin-5-yl)-7-methoxy-chromen-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 3-(2,4-dimethoxy-pyrimidin-5-yl)-7-methoxy-4-methyl-chromen-2-one (210 mg, 0.64 mmoL) in anhydrous THF (5 mL) at −78° C. was added LiHMDS (1.0 M, 1.28 mmoL, 1.28 mL) dropwise. The resulting reddish solution was stirred at −78° C. for 20 min. To this solution was added NBS (114 mg, 0.64 mmoL) in THF (2 mL) slowly. The reaction was stirred for 2 hours at −78° C. and then quenched with sat. NaHCO3, warmed to room temperature. THF was removed in vacuo and the residue was partitioned between CH2Cl2 and water. The aqueous phase was extracted 3× with CH2Cl2. The combined organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to afford a yellow solid, which was then purified by silica gel column chromatography using hexanes:ethyl acetate (4:1 to 2:1) to afford the title product as a white solid.

Workup

  1. stirringThe reaction was stirred for 2 hours at −78° C.
  2. customquenched with sat. NaHCO3
  3. temperaturewarmed to room temperature
  4. customTHF was removed in vacuo
  5. customthe residue was partitioned between CH2Cl2 and water
  6. extractionThe aqueous phase was extracted 3× with CH2Cl2
  7. washThe combined organic layer was washed with brine
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford a yellow solid, which
  12. customwas then purified by silica gel column chromatography

Sources & evidence

ORD record
ord-68e0ea85299c4c1986e6893cdc23ef51
Source dataset
uspto-grants-2008_07
Patent number
US07399767B2

Reaction notes

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