Pyridine → 3-Ethynyl-5-(pyrrolidin-1-ylmethyl)pyridine

HRID 1255919Notes

Reaction equation

HRID 1255919 reaction equation
CC1C=CC(C(O)=O)=CC=1[CH2:11][CH2:12][C:13]1[CH:14]=[N:15][CH:16]=[C:17]([CH2:19][N:20]2[CH2:24][CH2:23][CH2:22][CH2:21]2)[CH:18]=1.N1C=CC=CC=1.IC1C=C(C=CC=1C)C(O)=O.CCN(C(C)C)C(C)C>C(N(CC)CC)C.C(OCC)(=O)C.CN(C=O)C>[C:12]([C:13]1[CH:14]=[N:15][CH:16]=[C:17]([CH2:19][N:20]2[CH2:24][CH2:23][CH2:22][CH2:21]2)[CH:18]=1)#[CH:11]

Participants

8

Reactant 4

HCID 1049PyridineHCID 81531DiisopropylethylamineHCID 6216403-Iodo-4-methylbenzoic acidHCID 689092244-Methyl-3-{[5-(pyrrolidin-1-ylmethyl)pyridin-3-yl]ethyl}benzoic acid

Product 1

HCID 212559433-Ethynyl-5-(pyrrolidin-1-ylmethyl)pyridine

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-methyl-3-{[5-(pyrrolidin-1-ylmethyl)pyridin-3-yl]ethyl}benzoic acid can be prepared in a manner similar to that described above for the Sonogashira reaction. 3-Ethynyl-5-<pyrrolidin-1-ylmethyl)pyridine and 3-iodo-4-methylbenzoic acid are used as coupling partners. Alternatively, the solvent (DMF) can be replaced by ethyl acetate and the base (Hunig base) can be replaced by triethylamine. The product can be isolated by filtration of the crude reaction mixture. The filter cake is washed sequentially with a solvent such as ethyl acetate and then water, then dried in a vacuum oven. Further purification can be achieved by slurrying the solids in water adjusted to pH 3 with the addition of concentrated HCl. After filtration and water wash, the product can be dried in a vacuum oven.

Workup

  1. customthat described above for the Sonogashira reaction
  2. customThe product can be isolated by filtration of the crude
  3. customreaction mixture
  4. washThe filter cake is washed sequentially with a solvent such as ethyl acetate
  5. dry with materialwater, then dried in a vacuum oven
  6. customFurther purification
  7. additionadjusted to pH 3 with the addition of concentrated HCl
  8. filtrationAfter filtration and water
  9. washwash
  10. customthe product can be dried in a vacuum oven

Sources & evidence

ORD record
ord-ada22bc814f146efb886f8f3d2f4f4cb
Source dataset
uspto-grants-2013_06
Patent number
US08461167B2

Reaction notes

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