Methanol → 5-Bromo-4-chloro-2,6-dimethoxypyrimidine

HRID 426250Notes

Reaction equation

HRID 426250 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([O:10][CH3:11])[N:3]=1.C([O-])(O)=O.[Na+].CO.[Br:19]Br>O>[Br:19][C:7]1[C:2]([Cl:1])=[N:3][C:4]([O:10][CH3:11])=[N:5][C:6]=1[O:8][CH3:9]

Participants

6

Reactant 4

HCID 887MethanolHCID 24408BromineHCID 806004-Chloro-2,6-dimethoxypyrimidineHCID 516892Sodium Bicarbonate

Product 1

HCID 122261955-Bromo-4-chloro-2,6-dimethoxypyrimidineYield 86%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

In a 250 mL round bottom flask, 4-chloro-2,6-dimethoxy-pyrimidine (3.25 g, 18.65 mmol) and NaHCO3 (3.6 g, 42.9 mmol) was charged with MeOH and water (1:1 ratio, 160 mL). Bromine (1.44 mL, 27.97 mmol) was added to the mixture dropwise (in 1 hour). The reaction was stirred at room temperature overnight. The reaction mixture was concentrated down. Ethyl acetate was added, followed by washing with brine. The organic layer was concentrated down and purified (silica gel, 0-50% EtOAC/hexane) to give white solid (4.06 g, 86%). LC-MS shows 255.1 (M+1). 1H NMR (300 MHz, CDCl3): δ 4.07 (s, 3H), 3.98 (s, 3H); 13C NMR (300 MHz, CDCl3): δ 168.27; 162.79; 160.38; 97.08; 55.78; 55.70.

Workup

  1. concentrationThe reaction mixture was concentrated down
  2. additionEthyl acetate was added
  3. washby washing with brine
  4. concentrationThe organic layer was concentrated down
  5. custompurified (silica gel, 0-50% EtOAC/hexane)

Sources & evidence

ORD record
ord-fa59bf2d6afc418ab054551d750ff18a
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

Loading…