Benzyl Alcohol → 2-(Benzyloxy)pyridine-4-carboxylic acid

HRID 1097867Notes

Reaction equation

HRID 1097867 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([OH:7])=[O:6].[CH2:11]([OH:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[H-].[Na+].C1OCCOCCOCCOCCOCCOC1>C1(C)C=CC=CC=1>[C:12]1([CH2:11][O:18][C:2]2[CH:3]=[C:4]([C:5]([OH:7])=[O:6])[CH:8]=[CH:9][N:10]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 244Benzyl Alcohol2×HCID 24758Sodium hydride2×HCID 2855718-Crown-6HCID 2369852-Chloroisonicotinic acid2×

Product 1

HCID 229262722-(Benzyloxy)pyridine-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

2-Chloro-isonicotinic acid [CAS Reg. No. 6313-54-8] (4 g) and benzyl alcohol (3.3 g) were added to dry toluene (50 mL). Sodium hydride (2.66 g, 50% in mineral oil) was added in 2 portions and the mixture was allowed to stir at room temperature for 30 minutes. 18-Crown-6 (906 mg) was added and the mixture was then heated to 125° C. for 12 hours. An unstirrable, yellow mixture was obtained. This was diluted with more toluene (80 mL) and stirring was continued for another 4 hours at 125° C. TLC analysis confirmed that there was still 2-chloro-isonicotinic acid left. More benzyl alcohol (3.3 g) and sodium hydride was (2.66 g) added and the mixture was heated for another 12 hours. The mixture was cooled and quenched with 1M aqueous HCl (100 mL). Hexane (200 ml) was added and the mixture was stirred at 0° C. for 1 hour; a light brown solid was obtained. The solid was filtered off and washed with hexane. To remove residual water from the solid, toluene was added and removed again. A colorless solid was obtained (4.8 g). MS (m/e, ISP neg ion): 228.3 (M−H+).

Workup

  1. temperaturethe mixture was then heated to 125° C. for 12 hours
  2. customAn unstirrable, yellow mixture was obtained
  3. stirringstirring
  4. waitwas continued for another 4 hours at 125° C
  5. waitleft
  6. additionadded
  7. temperaturethe mixture was heated for another 12 hours
  8. temperatureThe mixture was cooled
  9. customquenched with 1M aqueous HCl (100 mL)
  10. additionHexane (200 ml) was added
  11. stirringthe mixture was stirred at 0° C. for 1 hour
  12. customa light brown solid was obtained
  13. filtrationThe solid was filtered off
  14. washwashed with hexane
  15. customTo remove residual water from the solid, toluene
  16. additionwas added
  17. customremoved again
  18. customA colorless solid was obtained (4.8 g)

Sources & evidence

ORD record
ord-daddfb714eb349a3a2ae2c011c89f23a
Source dataset
uspto-grants-2012_03
Patent number
US08143280B2

Reaction notes

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