Triethylamine → [2-Methoxy-4-methyl-6-(3-trifluoromethyl-phenyl)-pyridin-3-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone

HRID 1517068Notes

Reaction equation

HRID 1517068 reaction equation
[CH3:1][O:2][C:3]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[CH:9]=[C:8]([CH3:22])[C:4]=1[C:5](O)=[O:6].C(Cl)(=O)C(Cl)=O.CCN(CC)CC.[N:36]1([CH:41]2[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]2)[CH2:40][CH2:39][CH2:38][CH2:37]1>C(Cl)Cl.CN(C=O)C>[CH3:1][O:2][C:3]1[C:4]([C:5]([N:44]2[CH2:45][CH2:46][CH:41]([N:36]3[CH2:40][CH2:39][CH2:38][CH2:37]3)[CH2:42][CH2:43]2)=[O:6])=[C:8]([CH3:22])[CH:9]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:19])[F:20])[CH:13]=2)[N:11]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 787034-(1-Pyrrolidinyl)piperidineHCID 574411372-Methoxy-4-methyl-6-(3-trifluoromethyl-phenyl)-nicotinic acid

Product 1

HCID 57441138[2-Methoxy-4-methyl-6-(3-trifluoromethyl-phenyl)-pyridin-3-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanoneYield 97.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

A suspension of 0.200 g (0.64 mmol) 2-methoxy-4-methyl-6-(3-trifluoromethyl-phenyl)-nicotinic acid in 5 ml of CH2Cl2 was treated at RT with one drop of DMF; then, 0.06 ml=0.09 g (0.71 mmol) of oxalyl chloride was added to this solution drop by drop below 25° C. and the reaction mixture was stirred for 0.5 hour. After removal of the solvents by evaporation in a high vacuum, the residue was dissolved again in 10 ml of CH2Cl2 and 0.36 ml=0.26 g (2.57 mmol) of Et3N was added while stirring, followed by 0.099 g (0.64 mmol) of 4-pyrrolidin-1-yl-piperidine. The reaction mixture was stirred at RT. After 16 hours, it was poured into crashed ice and extracted twice with CH2Cl2; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 98:2 to 4:1) to give 0.278 g (97%) of the title compound as yellow amorphous solid. MS: 448.1 (MH+).

Workup

  1. customAfter removal of the solvents
  2. customby evaporation in a high vacuum
  3. dissolutionthe residue was dissolved again in 10 ml of CH2Cl2
  4. stirringwhile stirring
  5. stirringThe reaction mixture was stirred at RT
  6. waitAfter 16 hours
  7. additionit was poured
  8. extractionextracted twice with CH2Cl2
  9. washthe organic phases were washed with water
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. customevaporated
  13. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 98:2 to 4:1)

Sources & evidence

ORD record
ord-6e09e5d29fe94115af5bc0aeef12238a
Source dataset
uspto-grants-2012_07
Patent number
US08227613B2

Reaction notes

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