Water → Diethyl (pyrimidin-2-yl)propanedioate

HRID 1741280Notes

Reaction equation

HRID 1741280 reaction equation
[H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].Br[C:15]1[N:20]=[CH:19][CH:18]=[CH:17][N:16]=1.O>CN(C=O)C>[N:16]1[CH:17]=[CH:18][CH:19]=[N:20][C:15]=1[CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]([O:11][CH2:12][CH3:13])=[O:10]

Participants

6

Reactant 4

HCID 962WaterHCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 783452-Bromopyrimidine

Product 1

HCID 2303274Diethyl (pyrimidin-2-yl)propanedioateYield 49.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
100 °C

Procedure

To a solution of sodium hydride (4.4 g of a 60% dispersion in oil, 0.11 mol) in DMF (200 ml) was added diethyl malonate (16 ml, 0.11 mol) in DMF (50 ml) dropwise at room temperature. After 30 min 2-bromopyrimidine (8.0 g, 0.05 mol) was added portionwise and the solution heated at 100° C. for 3 h. The solution was cooled to room temperature, water (100 ml) was added and the mixture extracted with EtOAc (3×60 ml). The combined organic layers were dried (MgSO4) and evaporated. The residue was chromatographed on silica, using hexane:EtOAc (3:1) as the eluant, to afford the ester (5.9 g, 49%) as a pale yellow oil which solidified on standing at 0° C. 1H NMR (360 MHz, CDCl3) δ 1.29 (6H, t, J=7.1 Hz), 4.29 (4H, q, J=7.1 Hz), 5.10 (1H, s), 7.26 (1H, t, J=4.9 Hz), 8.74 (2H, d, J=4.9 Hz).

Workup

  1. temperatureThe solution was cooled to room temperature
  2. extractionthe mixture extracted with EtOAc (3×60 ml)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. customevaporated
  5. customThe residue was chromatographed on silica

Sources & evidence

ORD record
ord-dd2ee10f2f944345a70ef15bdcda938c
Source dataset
uspto-grants-1999_10
Patent number
US05973156

Reaction notes

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