Methyl bromoacetate → 5-Benzyloxy-1-methoxycarbonylmethyl-2-methylsulfanyl-6-oxo-1,6-dihydro-pyrimidine-4-carboxylic acid ethyl ester

HRID 458677

Reaction equation

HRID 458677 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([S:21][CH3:22])[NH:9][C:10](=[O:20])[C:11]=1[O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:5])[CH3:2].Br[CH2:24][C:25]([O:27][CH3:28])=[O:26].[H-].[Ca+2].[H-]>O1CCCC1>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([S:21][CH3:22])[N:9]([CH2:24][C:25]([O:27][CH3:28])=[O:26])[C:10](=[O:20])[C:11]=1[O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 60984Methyl bromoacetateHCID 3033859Calcium hydrideHCID 135772690HCID 135772690, compound

Product 1

HCID 588212315-Benzyloxy-1-methoxycarbonylmethyl-2-methylsulfanyl-6-oxo-1,6-dihydro-pyrimidine-4-carboxylic acid ethyl esterYield 45%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of intermediate 1, 5-benzyloxy-2-methylsulfanyl-6-oxo-1,6-dihydro-pyrimidine-4-carboxylic acid ethyl ester, (2.00 g, 6.24 mmol) in dry tetrahydrofuran (100 ml) was treated with methyl bromoacetate (1.05 g, 6.86 mmol) followed by powdered calcium hydride (0.59 g, 14.0 mmol) and the resulting mixture was heated under reflux for 18 h. The reaction mixture was then cooled, quenched by the addition of a few drops of acetic acid and concentrated in vacuo. The residue was then diluted with ethyl acetate, washed successively with saturated sodium bicarbonate and brine then dried over anhydrous magnesium sulfate. Evaporation of the solvent followed by chromatography on silica gel (elution toluene/ethyl acetate 95:5) gave 1.10 g (45% yield) of the title ester as a clear oil. 1HNMR 400 MHz (CDCl3) δ (ppm): 1.31 (3H, t, J=7.2 Hz, CH3), 2.60 (3H, s, SCH3), 3.80 (3H, s, OCH3), 4.33 (2H, q, J=7.2 Hz, OCH2), 4.84 (2H, s, NCH2), 5.21 (2H, s, OCH2), 7.3–7.5 (5H, m, aromatics). HRMS (FAB POS) calculated for C18H21N2O6S [M+H+]: 393.112033. found: 393.112070.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureunder reflux for 18 h
  3. temperatureThe reaction mixture was then cooled
  4. customquenched by the addition of a few drops of acetic acid
  5. concentrationconcentrated in vacuo
  6. additionThe residue was then diluted with ethyl acetate
  7. washwashed successively with saturated sodium bicarbonate and brine
  8. dry with materialthen dried over anhydrous magnesium sulfate
  9. customEvaporation of the solvent

Sources & evidence

ORD record
ord-1ee32bbbb8c34e8ebce296003698203a
Source dataset
uspto-grants-2007_03
Patent number
US07192948B2

Linked notes

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