(Trifluoromethyl)trimethylsilane → tert-Butyl 2-chloro-6-(2,2,2-trifluoro-1-hydroxyethyl)isonicotinate

HRID 1909135Notes

Reaction equation

HRID 1909135 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([CH:15]=[O:16])[N:14]=1)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[F:17][C:18]([Si](C)(C)C)([F:20])[F:19]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([CH:15]([OH:16])[C:18]([F:20])([F:19])[F:17])[N:14]=1)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6]

Participants

4

Reactant 2

HCID 552549(Trifluoromethyl)trimethylsilane2×HCID 86657032tert-Butyl 2-chloro-6-formylisonicotinate

Product 1

HCID 86657033tert-Butyl 2-chloro-6-(2,2,2-trifluoro-1-hydroxyethyl)isonicotinateYield 104.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl 2-chloro-6-formylisonicotinate (1.5 g, 6.2 mmol) in THF (40 mL) were added (trifluoromethyl)trimethylsilane (1.49 mL, 4.31 mmol) and ground 4 A° molecular sieves. The mixture was cooled to 0° C. and TBAP (1.0 M in THF; 1.86 mL, 1.86 mmol) was added dropwise. The mixture was warmed to ambient temperature. After 30 min, additional (trifluoromethyl)trimethylsilane (0.5 mL, 1.44 mmol), TBAP (1.0 M in THF; 0.62 mL, 0.62 mmol) and ground 4 A° molecular sieves were added. After 30 min, the mixture was filtered with Celite. Aqueous 1 N HCl was added to the filtrate and the filtrate was extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→95% hexanes/ethyl acetate) gave the title compound (1.4 g). MS 312.2 (M+1).

Workup

  1. temperatureThe mixture was warmed to ambient temperature
  2. additionwere added
  3. waitAfter 30 min
  4. filtrationthe mixture was filtered with Celite
  5. additionAqueous 1 N HCl was added to the filtrate
  6. extractionthe filtrate was extracted with ethyl acetate (3×)
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification by silica gel chromatography (100% hexanes→95% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-bd53e88742dc497ebea8bb6d4d274d73
Source dataset
uspto-grants-2013_12
Patent number
US08598209B2

Reaction notes

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