Hydrochloric Acid → 6-Cyclopropylmethoxy-5-trifluoromethyl-pyridine-2-carboxylic acid

HRID 632141

Reaction equation

HRID 632141 reaction equation
[H-].[Na+].[CH:3]1([CH2:6][OH:7])[CH2:5][CH2:4]1.C[O:9][C:10]([C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[C:14](Cl)[N:13]=1)=[O:11].Cl>O>[CH:3]1([CH2:6][O:7][C:14]2[N:13]=[C:12]([C:10]([OH:11])=[O:9])[CH:17]=[CH:16][C:15]=2[C:18]([F:21])([F:19])[F:20])[CH2:5][CH2:4]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 75644CyclopropanemethanolHCID 70701015Methyl 6-chloro-5-(trifluoromethyl)picolinate

Product 1

HCID 710874576-Cyclopropylmethoxy-5-trifluoromethyl-pyridine-2-carboxylic acidYield 85%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Sodium hydride (1.1 g, 31.4 mmol) was added in portions to cyclopropylmethanol (20 mL) and the mixture was stirred at room temperature for 0.5 hours. 6-Chloro-5-(trifluoromethyl)-pyridine-2-carboxylic acid methyl ester (1.5 g, 6.3 mmol) was added and the resulting solution was stirred at 80° C. for 1 h. Water (20 mL) was added; the solution was acidified with 6 N hydrochloric acid and then concentrated to give a residue which was partitioned between water (30 mL) and ethyl acetate (20 mL). The aqueous solution was extracted with ethyl acetate (2×20 mL) and the combined organic phase was washed with brine (20 mL), dried over anhydrous sodium sulfate, filtered and concentrated to give the crude target compound. The crude target compound was purified by column chromatography (silica gel, 10 g, 15% ethyl acetate in petroleum ether) to give the title compound (1.4 g, 85%) as white solid; MS (EI): m/e=262.0 [M+H]+.

Workup

  1. stirringthe resulting solution was stirred at 80° C. for 1 h
  2. concentrationconcentrated
  3. customto give a residue which
  4. customwas partitioned between water (30 mL) and ethyl acetate (20 mL)
  5. extractionThe aqueous solution was extracted with ethyl acetate (2×20 mL)
  6. washthe combined organic phase was washed with brine (20 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give the crude target compound
  11. customThe crude target compound was purified by column chromatography (silica gel, 10 g, 15% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-fb120d26a54e41be91b116d88a38ab99
Source dataset
uspto-grants-2016_04
Patent number
US09321727B2

Linked notes

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