Oxalyl chloride → [6-{3-[3,5-Bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl}-4-(trifluoromethyl)pyridin-3-yl]methanol

HRID 2206916Notes

Reaction equation

HRID 2206916 reaction equation
[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C:13]2([C:31]([F:34])([F:33])[F:32])[CH2:17][CH2:16][N:15]([C:18]3[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[C:21]([C:22](O)=[O:23])=[CH:20][N:19]=3)[CH2:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C(Cl)(=O)C(Cl)=O>C(Cl)Cl.CN(C)C=O>[F:36][C:2]([F:1])([F:35])[C:3]1[CH:4]=[C:5]([C:13]2([C:31]([F:32])([F:33])[F:34])[CH2:17][CH2:16][N:15]([C:18]3[N:19]=[CH:20][C:21]([CH2:22][OH:23])=[C:25]([C:27]([F:28])([F:29])[F:30])[CH:26]=3)[CH2:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

5

Reactant 2

HCID 65578Oxalyl chlorideHCID 871585506-{3-[3,5-Bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl}-4-(tri-fluoromethyl)nicotinic acid

Product 1

HCID 87158576[6-{3-[3,5-Bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl}-4-(trifluoromethyl)pyridin-3-yl]methanolYield 90.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

6-{3-[3,5-Bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl}-4-(trifluoromethyl)nicotinic acid (1.11 g) was dissolved in methylene chloride (30 ml), and to the solution was added oxalyl chloride (0.54 ml, 6.16 mmol) and one drop of dimethylformamide at room temperature. After stirring for 5 hours, the solvent and excess oxalyl chloride were distilled off under reduced pressure. The residue was dissolved in dioxane, added with water, and then added with sodium borohydride (0.23 g) at 0° C. The mixture was stirred for 2 hours at room temperature and added with diluted hydrochloric acid. The mixture was extracted with ethyl acetate, dried over magnesium sulfate and filtered. After concentration under reduced pressure, the target compound (0.98 g) was obtained by purification with silica gel column chromatography.

Workup

  1. distillationthe solvent and excess oxalyl chloride were distilled off under reduced pressure
  2. dissolutionThe residue was dissolved in dioxane
  3. additionadded with water
  4. additionadded with sodium borohydride (0.23 g) at 0° C
  5. stirringThe mixture was stirred for 2 hours at room temperature
  6. additionadded with diluted hydrochloric acid
  7. extractionThe mixture was extracted with ethyl acetate
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationAfter concentration under reduced pressure

Sources & evidence

ORD record
ord-63638f73d77845dd84d36eebf2e46953
Source dataset
uspto-grants-2016_06
Patent number
US09375000B2

Reaction notes

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