Morpholine → Methyl 2-chloro-6-morpholin-4-ylpyrimidine-4-carboxylate

HRID 1641265Notes

Reaction equation

HRID 1641265 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[C:9](Cl)[N:8]=[C:7]([Cl:12])[N:6]=1)=[O:4].[NH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.C(N(C(C)C)CC)(C)C>CS(C)=O.O>[Cl:12][C:7]1[N:6]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[CH:10]=[C:9]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[N:8]=1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 239689Methyl 2,4-dichloropyrimidine-6-carboxylate

Product 1

HCID 4356884Methyl 2-chloro-6-morpholin-4-ylpyrimidine-4-carboxylateYield 80.5%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a solution of 2,6-dichloropyrimidine-4-carboxylic acid methyl ester (300 mg, 1.45 mmol) in dimethylsulfoxide (2 ml) is added morpholine (0.126 g, 1.0 eq) followed by diisopropylethylamine (0.285 ml, 1.1 eq). The mixture is stirred at room temperature for 15 h before being diluted with water and extracted with ethyl acetate (2×20 ml). The combined organic layers are washed with water, dried over Na2SO4 and evaporated to dryness. The residue is purified by column chromatography on silica gel, eluted with ethyl acetate:hexane (1:1) to provide methyl 2-chloro-6-morpholin-4-ylpyrimidine-4-carboxylate as a white solid (0.30 g). Mp: 135-138° C., 1H NMR (300 MHz, DMSO-d6) δ 7.34 (s, 1H), 3.86 (s, 3H), 3.67 (brs, 8H). MS: 257 (M+1).

Workup

  1. extractionextracted with ethyl acetate (2×20 ml)
  2. washThe combined organic layers are washed with water
  3. dry with materialdried over Na2SO4
  4. customevaporated to dryness
  5. customThe residue is purified by column chromatography on silica gel
  6. washeluted with ethyl acetate:hexane (1:1)

Sources & evidence

ORD record
ord-8582e5582a074ef8889ab30a883a404a
Source dataset
uspto-grants-2012_02
Patent number
US08114873B2

Reaction notes

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