Water → HCID 86661726, compound

HRID 2284501Notes

Reaction equation

HRID 2284501 reaction equation
[F:1][C:2]([F:8])([F:7])[O:3][CH2:4][CH2:5][OH:6].Cl[C:10]1[N:18]=[C:17]([Cl:19])[C:16]([Cl:20])=[CH:15][C:11]=1[C:12]([NH2:14])=[O:13].C(O[K])(C)(C)C.O>CN(C=O)C.COCCOC.CCOC(C)=O>[Cl:20][C:16]1[C:17]([Cl:19])=[N:18][C:10]([O:6][CH2:5][CH2:4][O:3][C:2]([F:8])([F:7])[F:1])=[C:11]([CH:15]=1)[C:12]([NH2:14])=[O:13]

Participants

7

Reactant 4

HCID 962WaterHCID 179516872-(Trifluoromethoxy)ethan-1-olHCID 537509302,5,6-Trichloropyridine-3-carboxamideHCID 178418922HCID 178418922, compound

Product 1

HCID 86661726HCID 86661726, compoundYield 8%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 18463208dimethoxyethane N,N-dimethylformamideSolvent

Procedure

To a mixture of compound 2-(trifluoromethoxy)ethanol (9.5 mmol) in DMF/DME (20/50 mL) was added 2,5,6-trichloronicotinamide (2.1 g, 9.5 mmol) and tert-BuOK (1.30 g, 11.4 mmol) and the reaction mixture was stirred at room temperature overnight. The mixture was poured into 100 mL of cold water, diluted with 100 mL of EtOAc, the organic layer was separated and the aqueous phase was further extracted twice with EtOAc, the combined organic layers were washed with brine twice, dried over Na2SO4 and concentrated, the residue was purified by silica gel chromatography (Petroleum ether: EtOAc=1:0 to 5:1) to give 5,6-dichloro-2-(2-(trifluoromethoxy)ethoxy)nicotinamide (0.24 g, 8%). 1H-NMR (400 MHz, DMSO-d6) δ (ppm) 8.31 (s, 1H), 7.97 (s, 1H), 7.59 (s, 1H), 4.62 (t, 2H, J=4.0 Hz), 4.51 (t, 2H, J=4.0 Hz).

Workup

  1. customthe organic layer was separated
  2. extractionthe aqueous phase was further extracted twice with EtOAc
  3. washthe combined organic layers were washed with brine twice
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customthe residue was purified by silica gel chromatography (Petroleum ether: EtOAc=1:0 to 5:1)

Sources & evidence

ORD record
ord-d65ec4d15d66496e82c9b426375865a4
Source dataset
uspto-grants-2015_09
Patent number
US09145429B2

Reaction notes

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