4,6-Dichloropyrimidine → 2(2-(4,4-Dimethyl-oxazolin-2-yl)-benzyl)-4,6-dichloropyrimidine

HRID 863752Notes

Reaction equation

HRID 863752 reaction equation
[C:1]1([CH3:14])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[O:8][CH2:9][C:10]([CH3:13])([CH3:12])[N:11]=1.C([Li])CCC.[Cl:20][C:21]1[CH:26]=[C:25]([Cl:27])[N:24]=[CH:23][N:22]=1>CCOCC.CCCCCC>[CH3:13][C:10]1([CH3:12])[CH2:9][O:8][C:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=2[CH2:14][C:23]2[N:24]=[C:25]([Cl:27])[CH:26]=[C:21]([Cl:20])[N:22]=2)=[N:11]1

Participants

6

Reactant 3

HCID 709434,6-DichloropyrimidineHCID 104878894,4-Dimethyl-2-(2-methylphenyl)-4,5-dihydro-1,3-oxazoleHCID 178418339Butyllithium

Product 1

HCID 190506632(2-(4,4-Dimethyl-oxazolin-2-yl)-benzyl)-4,6-dichloropyrimidine

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 1.25 g of 2-o-tolyl-4,4-dimethyl-oxazoline in 20 ml of ether under N2 atmosphere at -30° C. is added by syringe 4.2 ml of 1.6M n-butyllithium in hexane with stirring which is continued for 1 hr at -10° C. 0.98 g of 4,6-dichloropyrimidine in 20 ml of ether are added slowly to the reaction mixture which is then stirred at -45° to -30° C. for 30 min and at 0° C. for a further 30 min. The reaction mixture is quenched with acetic acid (0.4 ml) and water (0.1 ml) in THF (1.3 ml) and then treated with 1.5 g of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in 6 ml of THF. The temperature is brought to RT and the mixture stirred for 5 min after cooling to 0° C. 7.6 ml of 1N NaOH (cooled) are added and the mixture stirred for 5 min. The organic phase is separated and dried over Na2SO4 filtered and the solvent removed. Following chromatography (10/90 ether/hexane) the title product is obtained.

Workup

  1. stirringis then stirred at -45° to -30° C. for 30 min and at 0° C. for a further 30 min
  2. customThe reaction mixture is quenched with acetic acid (0.4 ml) and water (0.1 ml) in THF (1.3 ml)
  3. additiontreated with 1.5 g of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in 6 ml of THF
  4. customis brought to RT
  5. stirringthe mixture stirred for 5 min
  6. addition7.6 ml of 1N NaOH (cooled) are added
  7. stirringthe mixture stirred for 5 min
  8. customThe organic phase is separated
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. customthe solvent removed
  12. customis obtained

Sources & evidence

ORD record
ord-e54b054fde0642d88b4cc2dd7349380c
Source dataset
uspto-grants-1996_10
Patent number
US05561101

Reaction notes

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