1-Propanol → HCID 22648221, compound

HRID 393898Notes

Reaction equation

HRID 393898 reaction equation
[Na].CCCCCC.Cl[C:9]1[N:17]=[CH:16][CH:15]=[CH:14][C:10]=1[C:11]([OH:13])=[O:12].[CH2:18]([OH:21])[CH2:19][CH3:20]>>[CH2:18]([O:21][C:9]1[N:17]=[CH:16][CH:15]=[CH:14][C:10]=1[C:11]([OH:13])=[O:12])[CH2:19][CH3:20]

Participants

5

Reactant 4

HCID 10311-Propanol2×HCID 8058HexaneHCID 762582-Chloronicotinic acidHCID 5360545Sodium

Product 1

HCID 22648221HCID 22648221, compound

Procedure

Sodium metal (9.2 g, 0.4 mol), washed free of oil (with hexane), was added in small pieces, over 2 h, to anhydrous n-propanol (350 mL) whilst maintaining a temperature between 50° C. and 100° C. To the resultant clear, yellow solution was added a slurry of 2-chloronicotinic acid (31.5 g, 0.2 mol) in anhydrous propanol (100 mL), and the suspension heated to reflux for 6 h. The bulk of the solvent was distilled off, and replaced, after cooling, with diethyl ether (200 mL) to afford a thick white solid which was removed by filtration and washed with diethyl ether (500 mL). The solid was taken up in water (300 mL), washed with dichloromethane (200 mL), and the aqueous phase acidified with concentrated hydrochloric acid to pH 4.5 and extracted with dichloromethane (3×200 mL). The combined extracts were washed with brine, dried over MgSO4, and concentrated to an oil (40 g). The oil was taken up in pentane (150 mL) and stood in ice for 30 mins to deliver a white crystalline solid which was collected by filtration, washed with fresh pentane (3×200 mL) and dried under vacuum to afford 2-propoxynicotinic acid (26.5 g, 146 mmol).

Workup

  1. temperaturewhilst maintaining a temperature between 50° C. and 100° C
  2. temperaturethe suspension heated
  3. temperatureto reflux for 6 h
  4. distillationThe bulk of the solvent was distilled off
  5. temperatureafter cooling, with diethyl ether (200 mL)
  6. customto afford a thick white solid which
  7. customwas removed by filtration
  8. washwashed with diethyl ether (500 mL)
  9. washwashed with dichloromethane (200 mL)
  10. extractionextracted with dichloromethane (3×200 mL)
  11. washThe combined extracts were washed with brine
  12. dry with materialdried over MgSO4
  13. concentrationconcentrated to an oil (40 g)
  14. filtrationwas collected by filtration
  15. washwashed with fresh pentane (3×200 mL)
  16. customdried under vacuum

Sources & evidence

ORD record
ord-4e996ed5fb454bbdb95655cd5ad6f220
Source dataset
uspto-grants-2004_10
Patent number
US06809200B2

Reaction notes

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