Water → 2-Chloro-6-ethylsulfanyl-5-fluoro-nicotinic acid ethyl ester

HRID 901246Notes

Reaction equation

HRID 901246 reaction equation
[CH2:1]([SH:3])[CH3:2].[H-].[Na+].[CH2:6]([O:8][C:9](=[O:19])[C:10]1[CH:15]=[C:14]([F:16])[C:13](Cl)=[N:12][C:11]=1[Cl:18])[CH3:7].O>C1COCC1>[CH2:6]([O:8][C:9](=[O:19])[C:10]1[CH:15]=[C:14]([F:16])[C:13]([S:3][CH2:1][CH3:2])=[N:12][C:11]=1[Cl:18])[CH3:7]

Participants

6

Reactant 4

HCID 962WaterHCID 6343EthanethiolHCID 24758Sodium hydrideHCID 13210747Ethyl 2,6-dichloro-5-fluoropyridine-3-carboxylate

Product 1

HCID 596996322-Chloro-6-ethylsulfanyl-5-fluoro-nicotinic acid ethyl esterYield 98.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Ethanethiol (15.08 mL, 204 mmol) was added slowly to a stirred suspension of NaH (60% in Mineral oil, 8.15 g, 204 mmol) in THF and stirred for 30 min at room temperature to yield a white thick suspension. This suspension was diluted by cold THF, cooled to 0° C. and transferred to an already cooled solution of 2,6-dichloro-5-fluoro-nicotinic acid ethyl ester (65) (48.5 g, 204 mmol) in THF at −20° C. under argon by maintaining the temperature below −10° C. The solution was stirred at −20° C. for 15 min and allowed to come at room temperature slowly. The solution was poured into water and extracted by ethyl acetate. The organic layer was dried over MgSO4 and concentrated under reduced pressure to yield 53 g (98%) of 2-chloro-6-ethylsulfanyl-5-fluoro-nicotinic acid ethyl ester (66) as brown liquid. 1H-NMR (DMSO-d6): δ 1.33 (m, 6H), 3.19 (q, J=7.2 Hz, 2H), 4.33 (q, J=7.2 Hz, 2H), 8.10 (d, J=9.6 Hz, 1H); EIMS m/z 264 (M+1).

Workup

  1. customto yield a white thick suspension
  2. temperaturecooled to 0° C.
  3. temperatureby maintaining the temperature below −10° C
  4. stirringThe solution was stirred at −20° C. for 15 min
  5. customto come at room temperature
  6. extractionextracted by ethyl acetate
  7. dry with materialThe organic layer was dried over MgSO4
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-85216706555a4a0193f5490520c37883
Source dataset
uspto-grants-2008_04
Patent number
US07361760B2

Reaction notes

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