Methane → (S)-2-Phthalimido-6-hydroxyhexanoic acid

HRID 1292656Notes

Reaction equation

HRID 1292656 reaction equation
[CH4:1].[C:2]([N:7]1[C:11](=[O:12])[C:10]2=[CH:13][CH:14]=[CH:15][CH:16]=[C:9]2[C:8]1=[O:17])(OCC)=O.[C:18](=[O:21])([O-])[O-:19].[Na+].[Na+]>[OH-].[Na+]>[C:8]1(=[O:17])[N:7]([C@@H:2]([CH2:1][CH2:9][CH2:10][CH2:11][OH:12])[C:18]([OH:19])=[O:21])[C:11](=[O:12])[C:10]2=[CH:13][CH:14]=[CH:15][CH:16]=[C:9]12

Participants

5

Reactant 3

HCID 297MethaneHCID 10340Sodium CarbonateHCID 31187N-Carbethoxyphthalimide

Product 1

HCID 11065730(S)-2-Phthalimido-6-hydroxyhexanoic acid

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent2×

Conditions

Temperature
35 °C

Procedure

The above crude reaction mixture was heated to 35° C. and treated with about 600 ml of 6N sodium hydroxide followed by 1N sodium hydroxide to adjust to pH of 7.5 (final volume was about 5.3 l). To this mixture was added 0.6 g of porcine kidney acylase I. After stirring overnight at 350C the pH was 7.25. The pH was adjusted to 7.5 and an additional 300 mg of acylase was added. After stirring overnight, the reaction appeared to be about 90% complete. The reaction mixture was next treated with 20 g of charcoal and 20 g of Celite®, then heated to 85° C. and maintained at that temperature for 10 minutes, then cooled to 50° C. and filtered. At this point, the total volume of the filtrate was about 4.9 l. The afiltrate was cooled to 5° C. and solid sodium carbonate was added to adjust the pH to 9.3. N-Carbethoxy-phthalimide (263.04 g, 1.2 mol) was added in one portion and sodium carbonate was added as needed to keep the pH at 9.3. After 2 hours at 5° C. followed by 3 hours at room temperature, the pH dropped to 8.5 and most of the reagents had dissolved. The reaction mixture was filtered, cooled to 5° C. and acidified to pH 2.3 with 6N hydrochloric acid. The precipitated solid was collected by filtration and washed with 200 ml of cold water, then dried in vacuo to yield 220 g of title product.

Workup

  1. customThe above crude reaction mixture
  2. additionTo this mixture was added 0.6 g of porcine kidney acylase I
  3. additionan additional 300 mg of acylase was added
  4. temperatureheated to 85° C.
  5. temperaturemaintained at that temperature for 10 minutes
  6. temperaturecooled to 50° C.
  7. filtrationfiltered
  8. temperatureThe afiltrate was cooled to 5° C.
  9. additionsolid sodium carbonate was added
  10. additionwas added
  11. waitAfter 2 hours at 5° C. followed by 3 hours at room temperature
  12. additionthe pH dropped to 8.5 and most of the reagents
  13. dissolutionhad dissolved
  14. filtrationThe reaction mixture was filtered
  15. temperaturecooled to 5° C.
  16. filtrationThe precipitated solid was collected by filtration
  17. washwashed with 200 ml of cold water
  18. customdried in vacuo

Sources & evidence

ORD record
ord-6fd96c475b2a4ec69ef784fc4c437dbe
Source dataset
uspto-grants-1998_05
Patent number
US05756832

Reaction notes

Loading…