Hydrochloric Acid → 1-[(2S)-1,4-Dioxan-2-ylmethyl]-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid

HRID 1428090Notes

Reaction equation

HRID 1428090 reaction equation
CS(O[CH2:6][C@H:7]1[CH2:12][O:11][CH2:10][CH2:9][O:8]1)(=O)=O.[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[C:21](=[O:31])[C:22]([C:26]([O:28]CC)=[O:27])=[CH:23][NH:24][CH:25]=2)=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[OH-].[Na+].Cl>CN(C=O)C.O>[O:8]1[CH2:9][CH2:10][O:11][CH2:12][C@@H:7]1[CH2:6][N:24]1[CH:25]=[C:20]([C:17]2[CH:16]=[CH:15][C:14]([F:13])=[CH:19][CH:18]=2)[C:21](=[O:31])[C:22]([C:26]([OH:28])=[O:27])=[CH:23]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 66771917Ethyl 5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxylateHCID 86609782(2R)-1,4-dioxan-2-ylmethyl methanesulfonate3×

Product 1

HCID 867000401-[(2S)-1,4-Dioxan-2-ylmethyl]-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acidYield 79.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(2R)-1,4-Dioxan-2-ylmethyl methanesulfonate (95 mg) was added to a suspension of ethyl 5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxylate (100 mg) and cesium carbonate (264 mg) in DMF (2 ml) at room temperature. The reaction mixture was stirred at room temperature overnight. (2R)-1,4-Dioxan-2-ylmethyl methanesulfonate (32 mg) was added at room temperature. The reaction mixture was stirred at 80° C. overnight. (2R)-1,4-Dioxan-2-ylmethyl methanesulfonate (32 mg) was added at room temperature. The reaction mixture was stirred at 100° C. for three hours and then returned to room temperature. A 1 N aqueous sodium hydroxide solution (2 ml) was added to the reaction mixture at room temperature. The reaction mixture was stirred at room temperature for one hour. A 1 N aqueous hydrochloric acid solution and water were added to the reaction mixture, and the precipitated solid was collected by filtration, washed with water and then dried to give 101 mg of the title compound as a solid.

Workup

  1. stirringThe reaction mixture was stirred at 80° C. overnight
  2. stirringThe reaction mixture was stirred at 100° C. for three hours
  3. customreturned to room temperature
  4. stirringThe reaction mixture was stirred at room temperature for one hour
  5. filtrationthe precipitated solid was collected by filtration
  6. washwashed with water
  7. customdried

Sources & evidence

ORD record
ord-88b5be09f2334afc834e3114d5b7086c
Source dataset
uspto-grants-2015_01
Patent number
US08933103B2

Reaction notes

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