Dichloromethane → (4-Chloro-5-fluoro-3-methoxypyridin-2-yl)cyclopropylacetonitrile

HRID 983401Notes

Reaction equation

HRID 983401 reaction equation
C(O[C:6]1[C:11]([F:12])=[CH:10][N:9]=[C:8]([CH:13]([CH:16]2[CH2:18][CH2:17]2)[C:14]#[N:15])[C:7]=1[O:19][CH3:20])(C)(C)C.FC(F)(F)C(O)=O.[Cl:28]CCl>>[Cl:28][C:6]1[C:11]([F:12])=[CH:10][N:9]=[C:8]([CH:13]([CH:16]2[CH2:18][CH2:17]2)[C:14]#[N:15])[C:7]=1[O:19][CH3:20]

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 10707715(4-tert-Butoxy-5-fluoro-3-methoxypyridin-2-yl)cyclopropylacetonitrile

Product 1

HCID 10562063(4-Chloro-5-fluoro-3-methoxypyridin-2-yl)cyclopropylacetonitrileYield 60%

Procedure

A solution of (4-tert-butoxy-5-fluoro-3-methoxypyridin-2-yl)cyclopropylacetonitrile (0.9 g, 3 mmol) [Example 8] and trifluoroacetic acid (2 mL) in dichloromethane was stirred at room temperature for 25 minutes. The solvent was removed in vacuo and the oily residue dissolved in 15 mL of dichloromethane and 2 mL of dimethylformamide. The resulting solution was cooled in an ice-bath and treated dropwise with phosphoryl chloride (2.4 mL). The solution was allowed to warm to ambient temperature and stirred overnight. The mixture was then poured onto ice and extracted with dichloromethane (2×20 mL). The combined extracts were washed with water, saturated sodium bicarbonate, water, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography, eluting with ethyl acetate/hexane (1:4) to provide the title compound (0.4 g, 60%). 1H NMR (400 MHz, CDCl3) δ 8.32 (s. 1H), 4.05 (s, 3H), 3.77 (d, 1H), 1.58-1.49 (m 1H), 0.80-0.71 (m, 1H), 0.68-0.55 (m, 2H), 0.52-0.43 (m, 1H). MSCI: m/z=241 (MH+).

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe oily residue dissolved in 15 mL of dichloromethane
  3. temperatureThe resulting solution was cooled in an ice-bath
  4. additiontreated dropwise with phosphoryl chloride (2.4 mL)
  5. additionThe mixture was then poured onto ice
  6. extractionextracted with dichloromethane (2×20 mL)
  7. washThe combined extracts were washed with water, saturated sodium bicarbonate, water
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography
  11. washeluting with ethyl acetate/hexane (1:4)

Sources & evidence

ORD record
ord-d877fb96454d4282b6bb67368bea99fb
Source dataset
uspto-grants-2005_03
Patent number
US06864259B2

Reaction notes

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