Ethyl chloroformate → HCID 9947173, compound

HRID 2183558Notes

Reaction equation

HRID 2183558 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]2[NH:13][C:12](=[O:14])[NH:11][C:10]([CH3:15])=[C:9]2[C:16]#[N:17])[CH:5]=[CH:6][CH:7]=1.[Li+].CC([N-]C(C)C)C.Cl[C:27]([O:29][CH2:30][CH3:31])=[O:28]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]2[N:13]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[C:12](=[O:14])[NH:11][C:10]([CH3:15])=[C:9]2[C:16]#[N:17])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 10928Ethyl chloroformateHCID 2724682Lithium diisopropylamideHCID 22473437HCID 22473437, compound

Product 1

HCID 9947173HCID 9947173, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of 6-(3-bromophenyl)-5-cyano-3,6-dihydro-4-methyl-2-oxo-(2H)-pyrimidine (0.29 g, 1 mmol) in THF (5 mL) chilled to −78° C. was added LDA (0.55 mL, 1.1 mmol, 2.0 M in THF). The resulting yellow suspension was stirred for 0.5 h, warmed to −20° C. for 0.5 h and recooled to −78° C.; then ethyl chloroformate (0.14 mL, 1.5 mmol) was added via syringe. The reaction mixture was stirred for 20 min, warmed to room temperature and quenched with EtOAc. This mixture was washed with aqueous NaHCO3 solution and with brine, dried (Na2SO4), and concentrated in vacuo. The residue was purified by flash column chromatography (10% to 30% EtOAc/hexanes) to give, after evaporation of solvent, 6-(3-bromophenyl)-5-cyano-3,6-dihydro-4-methyl-2-oxo-1-(2H)-pyrimidinecarboxylic acid, 1-ethyl ester as a colorless solid (0.29 g; 80%): 1H NMR (CDCl3, 400 MHz) δ 7.48 (m, 2H), 7.28 (m, 2H), 5.87 (s, 1H), 4.33 (m, 2H), 2.22 (s, 3H), 1.33 (t, 3H, J=7.0 Hz); LC/MS (ES+) 364 (M+H+).

Workup

  1. customrecooled to −78° C.
  2. stirringThe reaction mixture was stirred for 20 min
  3. temperaturewarmed to room temperature
  4. customquenched with EtOAc
  5. washThis mixture was washed with aqueous NaHCO3 solution and with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography (10% to 30% EtOAc/hexanes)
  9. customto give
  10. customafter evaporation of solvent, 6-(3-bromophenyl)-5-cyano-3,6-dihydro-4-methyl-2-oxo-1-(2H)-pyrimidinecarboxylic acid, 1-ethyl ester as a colorless solid (0.29 g; 80%)

Sources & evidence

ORD record
ord-915565ee56ac412dac1a5b3ddba92324
Source dataset
uspto-grants-2005_05
Patent number
US06900214B2

Reaction notes

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