Hydrochloric Acid → Methyl 2-(difluoromethyl)-5-(1-hydroxy-2-methylpropyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate

HRID 256807Notes

Reaction equation

HRID 256807 reaction equation
N1C=CC=[CH:3][C:2]=1[CH:7]=O.C([Mg]Cl)(C)C.[F:14][CH:15]([F:36])[C:16]1[C:21]([C:22]([O:24][CH3:25])=[O:23])=[C:20]([CH2:26][CH:27]([CH3:29])[CH3:28])[C:19]([CH:30]=[O:31])=[C:18]([C:32]([F:35])([F:34])[F:33])[N:17]=1.Cl>CCOCC.O>[F:36][CH:15]([F:14])[C:16]1[C:21]([C:22]([O:24][CH3:25])=[O:23])=[C:20]([CH2:26][CH:27]([CH3:29])[CH3:28])[C:19]([CH:30]([OH:31])[CH:2]([CH3:7])[CH3:3])=[C:18]([C:32]([F:35])([F:33])[F:34])[N:17]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 142732-PyridinecarboxaldehydeHCID 15107640Methyl 2-(difluoromethyl)-5-formyl-4-(2-methylpropyl)6-(trifluoromethyl)-3-pyridinecarboxylateHCID 178418918HCID 178418918, compound

Product 1

HCID 20098196Methyl 2-(difluoromethyl)-5-(1-hydroxy-2-methylpropyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×

Procedure

This example illustrates the preparation of Compound 14, an example of the condensation of a pyridine aldehyde and an organometallic reagent, followed by oxidation of the secondary alcohol. A solution of 2M isopropylmagnesium chloride in ether (40 mL) (Aldrich) was added in a slow stream to a solution of methyl 2-(difluoromethyl)-5-formyl-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate (7 g, 20 mmol) in anhydrous ether (30 mL) at -30° to -20° C. After the mixture was stirred for 3 h at <10° C., it was poured into iced water, acidified with conc. HCl, and extracted with methylene chloride. The organic extract was washed with brine, dried (MgSO4), and conc. to give 3 g of methyl 2-(difluoromethyl)-5-(1-hydroxy-2-methylpropyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate. A solution of this alcohol (3 g) in 20 mL of acetone Was cooled to <10° C., and 8N Jones' reagent (4 mL) was added dropwise. The mixture was stirred at RT for 24 h. Ether and water were added and the aqueous layer separated and extracted with ether. The combined ether layers were washed with water and brine, dried (MgSO4), and conc. in vacuo. The residue was purified by flash chromatography on silica gel with 8% ethyl acetate/cyclohexane to give 1.6 g of the desired compound as a light yellow solid, a yield of 21.1%. m.p. 45°-47° C.

Workup

  1. extractionextracted with methylene chloride
  2. extractionThe organic extract
  3. washwas washed with brine
  4. dry with materialdried (MgSO4)

Sources & evidence

ORD record
ord-9ed1f12e26354c8ca8e58a520320cf8d
Source dataset
uspto-grants-1993_11
Patent number
US05260262

Reaction notes

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