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

HRID 1872029Notes

Reaction equation

HRID 1872029 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-9891d888db7e40beb4876e2a26d55331
Source dataset
uspto-grants-2000_08
Patent number
US06107301

Reaction notes

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