Sodium hydride → HCID 66803248, compound

HRID 341528Notes

Reaction equation

HRID 341528 reaction equation
[H-].[Na+].[F:3][C:4]([F:8])([F:7])[CH2:5][SH:6].[CH3:9][O:10][C:11](=[O:19])[C:12]1[CH:17]=[CH:16][C:15](Cl)=[N:14][CH:13]=1>C1COCC1>[F:3][C:4]([F:8])([F:7])[CH2:5][S:6][C:15]1[N:14]=[CH:13][C:12]([C:11]([O:10][CH3:9])=[O:19])=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 41339242,2,2-Trifluoroethanethiol

Product 1

HCID 66803248HCID 66803248, compoundYield 98.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of sodium hydride (60% dispersion in mineral oil, 90 mg, 2.25 mmol) in anhydrous THF (40 mL) at 0 C was added 2,2,2-trifluoro-ethanethiol (200 μL, 2.25 mmol) drop-wise under nitrogen. The resulting solution was stirred for 15 min and added to a solution of 6-chloro-nicotinic acid methyl ester (257 mg, 1.5 mmol) in anhydrous THF (40 mL) at 0 C drop-wise. The reaction mixture was allowed to warm to room temperature and stirring was continued for a further 3 h. The solution was quenched with water at 0 C and extracted into EtOAc (3×50 mL). Combined organics were washed with brine (20 mL), dried over magnesium sulfate, evaporated to dryness and purified by silica chromatography (25% EtOAc in heptane) to afford the title compound as a colourless oil (370 mg, 98%). Method C HPLC-MS: MH+ requires m/z=252. Found: m/z=252, Rt=1.41 min (94%).

Workup

  1. stirringstirring
  2. waitwas continued for a further 3 h
  3. customThe solution was quenched with water at 0 C
  4. extractionextracted into EtOAc (3×50 mL)
  5. washCombined organics were washed with brine (20 mL)
  6. dry with materialdried over magnesium sulfate
  7. customevaporated to dryness
  8. custompurified by silica chromatography (25% EtOAc in heptane)

Sources & evidence

ORD record
ord-fee6fde8ee874ae59e06773bb8a7a040
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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