Methyl bromoacetate → 1-Benzyl-3-methoxycarbonyl-methyl-5-nitro-2,4(1H,3H)pyrimidinedione

HRID 990221Notes

Reaction equation

HRID 990221 reaction equation
[CH2:1]([N:8]1[CH:13]=[C:12]([N+:14]([O-:16])=[O:15])[C:11](=[O:17])[NH:10][C:9]1=[O:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:19]([O:22][C:23]([O-])=O)([O-])=[O:20].[K+].[K+].Br[CH2:29]C(OC)=O>CS(C)=O.O>[CH2:1]([N:8]1[C:13]([CH3:29])=[C:12]([N+:14]([O-:16])=[O:15])[C:11](=[O:17])[N:10]([C:19]([O:22][CH3:23])=[O:20])[C:9]1=[O:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 60984Methyl bromoacetateHCID 129887581-Benzyl-5-nitropyrimidine-2,4(1H,3H)-dioneHCID 86587255Potassium dicarbonate

Product 1

HCID 865872541-Benzyl-3-methoxycarbonyl-methyl-5-nitro-2,4(1H,3H)pyrimidinedioneYield 81%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

EX-1A) A solution of 1-benzyl-5-nitro-2,4(1H,3H) pyrimidinedione (6.14 g, 24.82 mmol) prepared as described by Vampa, G. and Pecorari P. Boll. Chim. Farm. 1987, 126, 467-469 was dissolved in 100 mL dimethylsulfoxide and potassium dicarbonate (3.78 g, 27.34 mmol) was added in one portion with stirring. After approximately 10 minutes a solution of methyl bromoacetate (2.50 mL, 26.40 mmol) in 20 mL dimethylsulfoxide was added drop wise over a 10 minute period. The reaction mixture was then heated to 40° C. and allowed to stir for 18 hours. The reaction mixture was diluted with water (500 mL). The aqueous solution was extracted with ethyl acetate (4×100 mL). The combined organic solutions were washed with water (1×150 mL), brine (2×150 mL). The organic solution was dried (MgSO4), filtered, and concentrated to give an oil. The crude oil was purified by MPLC (20% ethyl acetate/hexanes) to give pure 1-Benzyl-3-methoxycarbonyl -methyl-5-nitro-2,4(1H,3H)pyrimidinedione (EX-1A) as a white solid in 81% yield: 1H NMR (400 MHz, CDCl3) δ8.73 (s, 1H) 7.38-7.30 (m, 5H), 5.06 (s, 2H), 4.69 (s, 2H), 3.72 (s, 3H); HRMS (ES) calcd for C14H13N3O6 319.0804, found 319.0797.

Workup

  1. stirringto stir for 18 hours
  2. extractionThe aqueous solution was extracted with ethyl acetate (4×100 mL)
  3. washThe combined organic solutions were washed with water (1×150 mL), brine (2×150 mL)
  4. dry with materialThe organic solution was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give an oil
  8. customThe crude oil was purified by MPLC (20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-278bb2aa85ff4a0d9638daf9e582fa99
Source dataset
uspto-grants-2002_10
Patent number
US06458952B1

Reaction notes

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