Chlorotrimethylsilane → 2-Methoxy-5-trifluoromethyl-3-trimethylsilanyl-pyridine

HRID 1976047Notes

Reaction equation

HRID 1976047 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][N:16]=1.[CH3:25][Si:26](Cl)([CH3:28])[CH3:27]>O1CCCC1>[CH3:13][O:14][C:15]1[C:20]([Si:26]([CH3:28])([CH3:27])[CH3:25])=[CH:19][C:18]([C:21]([F:24])([F:22])[F:23])=[CH:17][N:16]=1

Participants

6

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 7912DiisopropylamineHCID 27753122-Methoxy-5-(trifluoromethyl)pyridineHCID 178418339Butyllithium

Product 1

HCID 220001752-Methoxy-5-trifluoromethyl-3-trimethylsilanyl-pyridineYield 48.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To butyl lithium (7.2 ml, 1.6M in hexanes, 11.5 mmol) in tetrahydrofuran (12.0 ml) at −78° C. was slowly added diisopropylamine (1.14 g, 11.3 mmol) in tetrahydrofuran (4.0 ml), and the resulting solution allowed to warm to 0° C. over 45 mins. A mixture of 2-methoxy-5-trifluoromethylpyridine (2.00 g, 11.3 mmol) and trimethylsilyl chloride (3.2 ml, 25.2 mmol) in tetrahydrofuran (8.0 ml) was then slowly added and the mixture stirred for 30 mins. at 0° C., before being quenched with water (50 ml). The mixture formed was extracted with ethyl acetate (2×70 ml), and the extracts washed with brine (50 ml), dried (Na2SO4) and concentrated to give the product as an orange oil (1.36 g, 48% yield).

Workup

  1. customat −78° C.
  2. additionwas then slowly added
  3. customat 0° C., before being quenched with water (50 ml)
  4. customThe mixture formed
  5. extractionwas extracted with ethyl acetate (2×70 ml)
  6. washthe extracts washed with brine (50 ml)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-70dba51a464240fca265d37a24206a8d
Source dataset
uspto-grants-2001_05
Patent number
US06225320B1

Reaction notes

Loading…