Hydrochloric Acid → HCID 89874898, compound

HRID 715444Notes

Reaction equation

HRID 715444 reaction equation
[F:1][C:2]([F:6])([F:5])[CH2:3][OH:4].C(=O)([O-])[O-].[Cs+].[Cs+].Cl.[Cl:14][C:15]1[C:16]([CH2:26]Cl)=[N:17][CH:18]=[C:19]([CH:25]=1)[C:20]([O:22]CC)=[O:21].[OH-].[Na+].Cl>CN(C=O)C.C1COCC1.O>[Cl:14][C:15]1[C:16]([CH2:26][O:4][CH2:3][C:2]([F:6])([F:5])[F:1])=[N:17][CH:18]=[C:19]([CH:25]=1)[C:20]([OH:22])=[O:21]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 64092,2,2-TrifluoroethanolHCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 71744190Ethyl 5-chloro-6-(chloromethyl)pyridine-3-carboxylate--hydrogen chloride (1/1)

Product 1

HCID 89874898HCID 89874898, compoundYield 99.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 2,2,2-trifluoroethanol (2.66 g, 26.6 mmol) and cesium carbonate (5.78 g, 17.7 mmol) in DMF (22 mL) is added ethyl 5-chloro-6-(chloromethyl)nicotinate hydrochloride (1.20 g, 4.44 mmol). After stirring at rt for 1 hour, 2 M aqueous sodium hydroxide solution (10 mL), water (20 mL), and THF (20 mL) are added to the mixture. After stirring at 60° C. for 2 hours, the mixture is acidified by 2 M hydrochloric acid (pH 4). The organic solvent is removed by evaporation, and the residual aqueous layer is extracted with EtOAc/hexane. The separated organic layer is dried over sodium sulfate, and after filtration, the filtrate is concentrated in vacuo to give 1.19 g (>99%) of the title compound as brown solid.

Workup

  1. stirringAfter stirring at 60° C. for 2 hours
  2. customThe organic solvent is removed by evaporation
  3. extractionthe residual aqueous layer is extracted with EtOAc/hexane
  4. dry with materialThe separated organic layer is dried over sodium sulfate
  5. filtrationafter filtration
  6. concentrationthe filtrate is concentrated in vacuo

Sources & evidence

ORD record
ord-153b5259388d44bb91655de2010f9154
Source dataset
uspto-grants-2015_11
Patent number
US09187475B2

Reaction notes

Loading…