Morpholine → 4-(2-chloro-6-methylpyrimidin-4-yl)morpholine

HRID 1251474Notes

Reaction equation

HRID 1251474 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([CH3:9])[N:3]=1.[NH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1.C(N(CC)C(C)C)(C)C>C(O)C>[Cl:1][C:2]1[N:7]=[C:6]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH:5]=[C:4]([CH3:9])[N:3]=1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 794712,4-Dichloro-6-methylpyrimidineHCID 81531Diisopropylethylamine

Product 1

HCID 31569994-(2-chloro-6-methylpyrimidin-4-yl)morpholineYield 72.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
25 °C

Procedure

Part A: A mixture of 2,4-dichloro-6-methylpyrimidine (4 g, 24.54 mmoles), morpholine (2.14 mL, 24.54 mmoles) and N,N-diisopropylethylamine (4.52 mL) in ethanol (60 mL) was stirred at 0° C. for 3 hours, 25° C. for 24 hours, followed by reflux for 1 hour. The solvent was removed under vacuum and the residue was partitioned between ethyl acetate (200 mL) and aq. sodium hydroxide (1 M, 50 mL). The organic layer was washed with water and brine and dried and concentrated in vacuo. The residue was recrystallized from ethyl acetate/hexanes to give 2-chloro-4-morpholino-6-methylpyrimidine (3.8 g).

Workup

  1. temperatureby reflux for 1 hour
  2. customThe solvent was removed under vacuum
  3. customthe residue was partitioned between ethyl acetate (200 mL) and aq. sodium hydroxide (1 M, 50 mL)
  4. washThe organic layer was washed with water and brine
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customThe residue was recrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-393fa82113034178a1f657b4edcfbce7
Source dataset
uspto-grants-2002_01
Patent number
US06342503B1

Reaction notes

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