Hydrochloric Acid → Salcaprozic acid

HRID 1738585Notes

Reaction equation

HRID 1738585 reaction equation
[OH-].[Na+].[C:3]1(=[O:12])[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]C[NH:4]1.N[CH:14]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[C:15]([OH:17])=[O:16].NCCCCCCCC(O)=[O:33].Cl>O.O1CCOCC1>[C:3]([NH:4][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:14][C:15]([OH:17])=[O:16])(=[O:12])[C:11]1[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=1)[OH:33]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 13632Octahydro-2H-azonin-2-oneHCID 14798Sodium HydroxideHCID 660858-Aminooctanoic acidHCID 695222-Aminooctanoic acid

Product 1

HCID 158789Salcaprozic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
25 °C

Procedure

Sodium hydroxide (1.68 g, 42.0 mmol, 1.2 eq), 2-azacyclononanone (5.0 g, 35.5 mmol, 1.0 eq) and 20 mL of water were placed a 100 mL round bottom flask equipped with a magnetic stir bar and cold water condenser to prepare aminocaprylic acid. The reaction mixture was heated to reflux for 2.5 hours (at which time the reaction was determined to have finished, by TLC) and cooled to 25 degrees C. A solution of oligosalicylate (4.87 g, 40 mmol, 1.1 eq) and dioxane (50 mL) was added to the aqueous solution of 8-aminocaprylic acid. This mixture was heated to reflux for 2.25 hours (at which time the reaction was determined to have finished, by HPLC). The clear orange reaction mixture was cooled to 25 degrees C. and acidified to pH=1 with 3% (by vol.) aqueous hydrochloric acid. All the dioxane and some of the water were stripped (60 degrees C., 50 min). The aqueous phase was decanted from the brown oil while still warm. Crystallization of the oil from ethanol-water yielded a white precipitate. The solid was recovered by filtration and was dried over 4 hours in a 50 degrees C. vacuum oven. The N-(salicyloyl)-8-aminocaprylic acid was isolated as a white solid (5.73 g, 59%).

Workup

  1. customequipped with a magnetic stir bar and cold water condenser
  2. temperatureThe reaction mixture was heated
  3. temperatureto reflux for 2.5 hours (at which time the reaction
  4. temperatureThis mixture was heated
  5. temperatureto reflux for 2.25 hours (at which time the reaction
  6. temperatureThe clear orange reaction mixture was cooled to 25 degrees C
  7. custom(60 degrees C., 50 min)
  8. customThe aqueous phase was decanted from the brown oil
  9. temperaturewhile still warm
  10. customCrystallization of the oil from ethanol-water
  11. customyielded a white precipitate
  12. filtrationThe solid was recovered by filtration
  13. customwas dried over 4 hours in a 50 degrees C

Sources & evidence

ORD record
ord-9084a8a6b34f42c5abf487bd72bec8a6
Source dataset
uspto-grants-1999_10
Patent number
US05962710

Reaction notes

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