4-Methylmorpholine → (R)-3-{4-[4-(3-cyclopropyl-5-methylpyridin-2-yl)piperazine-1-carbonyl]phenyl}-4-methyloxazolidin-2-one hydrochloride

HRID 1804207Notes

Reaction equation

HRID 1804207 reaction equation
[CH3:1][C@@H:2]1[CH2:6][O:5][C:4](=[O:7])[N:3]1[C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=1.[ClH:17].[CH:18]1([C:21]2[C:22]([N:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)=[N:23][CH:24]=[C:25]([CH3:27])[CH:26]=2)[CH2:20][CH2:19]1.O.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.CN1CCOCC1.[OH-].[Na+]>C(Cl)(Cl)Cl.CO>[ClH:17].[CH:18]1([C:21]2[C:22]([N:28]3[CH2:33][CH2:32][N:31]([C:12]([C:11]4[CH:10]=[CH:9][C:8]([N:3]5[C@H:2]([CH3:1])[CH2:6][O:5][C:4]5=[O:7])=[CH:16][CH:15]=4)=[O:14])[CH2:30][CH2:29]3)=[N:23][CH:24]=[C:25]([CH3:27])[CH:26]=2)[CH2:19][CH2:20]1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 14798Sodium HydroxideHCID 231494114-(4,6-Dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrateHCID 58484719(R)-4-(4-methyl-2-oxooxazolidin-3-yl)benzoic acidHCID 673807751-(3-Cyclopropyl-5-methylpyridin-2-yl)piperazine hydrochloride

Product 1

HCID 67381384(R)-3-{4-[4-(3-cyclopropyl-5-methylpyridin-2-yl)piperazine-1-carbonyl]phenyl}-4-methyloxazolidin-2-one hydrochlorideYield 83.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

(R)-4-(4-methyl-2-oxooxazolidin-3-yl)benzoic acid (442 mg) described in Preparation Example 37, 1-(3-cyclopropyl-5-methylpyridin-2-yl)piperazine hydrochloride (435 mg) described in Preparation Example 48 and 4-(4,6-dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (DMT-MM) (829 mg) were dissolved in chloroform (3 mL) and methanol (3 mL), N-methylmorpholine (220 μL) was added, and the mixture was stirred at room temperature overnight. To the reaction mixture was added 1N aqueous sodium hydroxide solution, and the mixture was extracted with chloroform. The organic layer was washed with saturated brine, and the solvent was evaporated. The residue was purified by column chromatography (hexane:ethyl acetate). The obtained compound was dissolved in ethyl acetate (20 mL), 4N hydrogen chloride/ethyl acetate (0.5 mL) was added, and the mixture was filtered to give the title compound (652 mg).

Workup

  1. extractionthe mixture was extracted with chloroform
  2. washThe organic layer was washed with saturated brine
  3. customthe solvent was evaporated
  4. customThe residue was purified by column chromatography (hexane:ethyl acetate)
  5. dissolutionThe obtained compound was dissolved in ethyl acetate (20 mL)
  6. addition4N hydrogen chloride/ethyl acetate (0.5 mL) was added
  7. filtrationthe mixture was filtered

Sources & evidence

ORD record
ord-15db2adbff2b46d48e95c23a89a32d9f
Source dataset
uspto-grants-2013_01
Patent number
US08354401B2

Reaction notes

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