Hydrochloric Acid → HCID 22605349, compound

HRID 2307256Notes

Reaction equation

HRID 2307256 reaction equation
C(N(CC)CC)C.Br[C:9]1[CH:10]=[N:11][C:12]([O:18][CH2:19][CH3:20])=[C:13]([CH:17]=1)[C:14]([OH:16])=[O:15].[CH:21]([O:23]CCCC)=[CH2:22].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.Cl>C(#N)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:21]([C:9]1[CH:10]=[N:11][C:12]([O:18][CH2:19][CH3:20])=[C:13]([CH:17]=1)[C:14]([OH:16])=[O:15])(=[O:23])[CH3:22]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8108Butyl vinyl etherHCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 226053205-Bromo-2-ethoxypyridine-3-carboxylic acid

Product 1

HCID 22605349HCID 22605349, compoundYield 63%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

Triethylamine (354 ml, 2.54 mol), was added to a slurry of 5-bromo-2-ethoxynicotinic acid (250 g, 1.02 mol) in acetonitrile (1 L). To this reaction mixture was added palladium (II) acetate (4.56 g, 20.3 mmol), butyl vinyl ether (305 g, 3.05 mol) and tri-o-tolyl phosphine (12.4 g, 40.6 mmol), each addition being washed in with acetonitrile. Further acetonitrile (1 L) was then added and the reaction mixture heated to reflux under nitrogen for 22 hours. The reaction mixture was left at room temperature for 16 hours, and then the precipitate removed by filtration. The filtrate was concentrated in vacuo to give a brown gum, which was then stirred for 1 hour in water (1 L) and concentrated HCl (1 L). The reaction mixture was diluted with water (6.25 L), and extracted with dichloromethane (6×500 mL). The combined organic layers were extracted with 5% sodium bicarbonate solution (1.2 L, 2×400 ml). The basic aqueous extracts were washed with dichloromethane (250 ml), and then acidified to pH 3. After stirring for 30 minutes the precipitated product was removed by filtration, washed with water (250 ml) and dried at 50° C. in vacuo to yield the target compound as a white solid (134 g, 64.1 mmol, 63%).

Workup

  1. additioneach addition
  2. washbeing washed in with acetonitrile
  3. additionFurther acetonitrile (1 L) was then added
  4. temperaturethe reaction mixture heated
  5. temperatureto reflux under nitrogen for 22 hours
  6. customthe precipitate removed by filtration
  7. concentrationThe filtrate was concentrated in vacuo
  8. customto give a brown gum, which
  9. extractionextracted with dichloromethane (6×500 mL)
  10. extractionThe combined organic layers were extracted with 5% sodium bicarbonate solution (1.2 L, 2×400 ml)
  11. washThe basic aqueous extracts were washed with dichloromethane (250 ml)
  12. customwas removed by filtration
  13. washwashed with water (250 ml)
  14. customdried at 50° C. in vacuo

Sources & evidence

ORD record
ord-45fed0cf4ec442d9b30d424c6132faa9
Source dataset
uspto-grants-2004_12
Patent number
US06831074B2

Reaction notes

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