Thionyl Chloride → HCID 49870021, compound

HRID 1519051Notes

Reaction equation

HRID 1519051 reaction equation
[Cl:1][C:2]1[C:7](=[O:8])[C:6]([OH:9])=[C:5]([CH:10](O)[C:11]([F:14])([F:13])[F:12])[N:4]([CH3:16])[C:3]=1[CH3:17].S(Cl)(Cl)=O.[BH4-].[Na+]>C(#N)C.CO>[Cl:1][C:2]1[C:7](=[O:8])[C:6]([OH:9])=[C:5]([CH2:10][C:11]([F:12])([F:13])[F:14])[N:4]([CH3:16])[C:3]=1[CH3:17]

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 4311764Sodium borohydrideHCID 70805135HCID 70805135, compound

Product 1

HCID 49870021HCID 49870021, compoundYield 61.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

3-Chloro-5-hydroxy-1,2-dimethyl-6-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4(1H)-one (300 mg, 1.10 mmol) was suspended in 10 mL of acetonitrile and thionyl chloride (398 μL, 5.50 mmol) was added dropwise. The reaction was stirred at room temperature. After 2 hours, the reaction was concentrated. The crude was diluted with 10 mL of methanol and sodium borohydride (329 mg, 8.80 mmol) was added in small portions. After 15 hours, the reaction was filtered and the filtrate was concentrated in vacuo. The resulting solid was dissolved in methanol and ethyl acetate added, filtered and concentrated. The crude product was purified by column chromatography on silica gel using a mixture of 30% EtOAc in MeOH as eluant. Fractions rich in product were combined and evaporated to dryness. The residue product was recrystallised from methanol/ethyl acetate to give 3-chloro-5-hydroxy-1,2-dimethyl-6-(2,2,2-trifluoroethyl)pyridin-4(1H)-one (172 mg) as a white solid. Yield=61%; 1H NMR (MeOD-D4, 90 MHz) δ (ppm): 4.1 (q, J=9.0 Hz, 2H), 3.99 (s, 3H) and 2.77 (s, 3H); MS m/z 256 [M+1]+.

Workup

  1. concentrationthe reaction was concentrated
  2. additionwas added in small portions
  3. waitAfter 15 hours
  4. filtrationthe reaction was filtered
  5. concentrationthe filtrate was concentrated in vacuo
  6. dissolutionThe resulting solid was dissolved in methanol
  7. additionethyl acetate added
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by column chromatography on silica gel using
  11. additiona mixture of 30% EtOAc in MeOH as eluant
  12. customevaporated to dryness
  13. customThe residue product was recrystallised from methanol/ethyl acetate

Sources & evidence

ORD record
ord-2bb3609a3d094ab0be1fe0a64a3c6d7e
Source dataset
uspto-grants-2015_07
Patent number
US09073865B2

Reaction notes

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