Hydrochloric Acid → 2-(1-Benzylpiperidin-4-ylamino)nicotinic acid

HRID 588047Notes

Reaction equation

HRID 588047 reaction equation
Cl[C:2]1[N:9]=[CH:8][CH:7]=[CH:6][C:3]=1C#N.[C:10](=[O:13])([O-])[O-:11].[K+].[K+].[NH2:16][CH:17]1[CH2:22][CH2:21][N:20]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:19][CH2:18]1.Cl>C1(C)C(C)=CC=CC=1.O.C(OCC)(=O)C>[CH2:23]([N:20]1[CH2:21][CH2:22][CH:17]([NH:16][C:2]2[N:9]=[CH:8][CH:7]=[CH:6][C:3]=2[C:10]([OH:11])=[O:13])[CH2:18][CH2:19]1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 810792-ChloronicotinonitrileHCID 4158521-Benzyl-4-piperidylamine

Product 1

HCID 714965982-(1-Benzylpiperidin-4-ylamino)nicotinic acidYield 71.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 7237O-XyleneSolventHCID 8857Ethyl AcetateSolvent

Procedure

In 500 ml of ortho-xylene, 100 g of 2-chloronicotinonitrile, 108.82 g of anhydrous potassium carbonate, and 133.83 ml of 4-amino-1-benzylpiperidine were together stirred for 24 hrs under reflux. This reaction mixture was cooled to room temperature, added with 500 ml of ethyl acetate and 1,000 ml of pure water, and adjusted to a pH of about 2-3 with conc. HCl. The aqueous fraction thus formed was obtained, washed again with 300 ml of ethylacetate, and adjusted to a pH of about 9-10 with sodium hydroxide in an ice bath while stirring. After completion of addition of sodium hydroxide, the fraction was stirred for an additional 1 hr, filtered, washed with water, and hot air dried to afford 137.4 g of the title compound (yield: 71.5%). 1H NMR (CDCl3) δ 8.26 (dd, 1H), 7.63 (dd, 1H), 7.36-7.28 (m, 5H), 6.59 (m, 1H), 5.0 (d, 1H), 4.14-3.97 (m, 1H), 3.53 (s, 2H), 2.88 (d, 2H), 2.22 (t, 2H), 2.1-1.98 (m, 2H), 1.68-1.47 (m, 2H) ppm.

Workup

  1. temperatureunder reflux
  2. customThe aqueous fraction thus formed
  3. customwas obtained
  4. washwashed again with 300 ml of ethylacetate
  5. customadjusted to a pH of about 9-10 with sodium hydroxide in an ice bath
  6. additionAfter completion of addition of sodium hydroxide
  7. stirringthe fraction was stirred for an additional 1 hr
  8. filtrationfiltered
  9. washwashed with water, and hot air
  10. customdried

Sources & evidence

ORD record
ord-73ce13c0a7974c62a5f6ee378fe1a83e
Source dataset
uspto-grants-2016_01
Patent number
US09227955B2

Reaction notes

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