Ethanol → 6-(4-Chloro-phenyl)-5-cyclopropylmethoxy-pyridine-2-carboxylic acid

HRID 1528374Notes

Reaction equation

HRID 1528374 reaction equation
C(Cl)(=[O:3])C.[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:17]=C(C#N)[CH:15]=[CH:14][C:13]=2[O:20][CH2:21][CH:22]2[CH2:24][CH2:23]2)=[CH:8][CH:7]=1.[CH2:25]([OH:27])[CH3:26]>>[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:17]=[C:26]([C:25]([OH:3])=[O:27])[CH:15]=[CH:14][C:13]=2[O:20][CH2:21][CH:22]2[CH2:24][CH2:23]2)=[CH:8][CH:7]=1

Participants

4

Reactant 3

HCID 702EthanolHCID 6367Acetyl chlorideHCID 666786996-(4-Chloro-phenyl)-5-cyclopropylmethoxy-pyridine-2-carbonitrile

Product 1

HCID 666786056-(4-Chloro-phenyl)-5-cyclopropylmethoxy-pyridine-2-carboxylic acidYield 70.31%

Conditions

Temperature
90 °C

Procedure

8.27 g acetylchloride was added dropwise to 120 mL ethanol at 0° C. After 5 minutes, 6 g 6-(4-chloro-phenyl)-5-cyclopropylmethoxy-pyridine-2-carbonitrile was added at 0° C. The reaction mixture was stirred at 90° C. over 20 h. The reaction mixture was partitioned between water and ethyl acetate; then extracted. The organic phase was washed with brine; then dried over MgSO4. The crude product was stirred at room temperature in tetrahydrofuran:water 45:20. 1.77 g lithium hydroxide was added. The reaction mixture was stirred at 80° C. over 7 hours. The reaction mixture was added over acetic acid and extracted with dichloromethane. The organic phase was washed with water; then dried over MgSO4 and purified by chromatography on silica gel with a gradient of heptane to heptane:ethyl acetate 2:1 to yield 4.50 g (70.31%) of the title compound as light yellow solid, MS 304.1 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between water and ethyl acetate
  2. extractionthen extracted
  3. washThe organic phase was washed with brine
  4. dry with materialthen dried over MgSO4
  5. stirringThe crude product was stirred at room temperature in tetrahydrofuran:water 45:20
  6. addition1.77 g lithium hydroxide was added
  7. stirringThe reaction mixture was stirred at 80° C. over 7 hours
  8. additionThe reaction mixture was added over acetic acid
  9. extractionextracted with dichloromethane
  10. washThe organic phase was washed with water
  11. dry with materialthen dried over MgSO4
  12. custompurified by chromatography on silica gel with a gradient of heptane to heptane:ethyl acetate 2:1

Sources & evidence

ORD record
ord-9c364f12507f4347b85c161e14f71ac8
Source dataset
uspto-grants-2015_07
Patent number
US09090599B2

Reaction notes

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