Sodium → HCID 22025455, compound

HRID 733252Notes

Reaction equation

HRID 733252 reaction equation
[Na].[Cl-].NC(N)=[NH2+].[Cl:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][C:16]=1[Cl:17])[CH:13]([CH2:18][C:19]([O:21]CC)=[O:20])[N:12]([CH2:24][CH:25]([CH3:27])[CH3:26])[C:11]2=[O:28]>C(O)C>[Cl:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][C:16]=1[Cl:17])[CH:13]([CH2:18][C:19]([OH:21])=[O:20])[N:12]([CH2:24][CH:25]([CH3:26])[CH3:27])[C:11]2=[O:28]

Participants

5

Reactant 3

HCID 5360545Sodium2×HCID 5460839Carbamimidoylazanium ChlorideHCID 86591368HCID 86591368, compound

Product 1

HCID 22025455HCID 22025455, compoundYield 42.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
20 °C

Procedure

0.09 g of sodium is added to 5 cm3 of absolute ethanol under an inert atmosphere. After the sodium has totally disappeared, 0.04 g of guanidinium chloride is added. The reaction mixture is stirred under an inert atmosphere at a temperature in the region of 20° C. for 1.5 hours, followed by addition of a solution of 0.93 g of ethyl (5,6-dichloro-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetate in 10 cm3 of absolute ethanol. The reaction mixture is stirred at a temperature in the region of 20° C. for 18 hours and is then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is taken up in a mixture of 5 cm3 of water and 15 cm3 of diethyl ether and is then stirred at a temperature in the region of 20° C. for 1 hour. The mixture is concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is taken up in a mixture of dichloromethane and ethyl acetate and then filtered. The filtrate is purified by chromatography under argon pressure (80 kPa), on a cartridge of silica gel (particle size 32-63 μm), eluting with a mixture of dichloromethane/methanol (95/5 by volume). The fractions comprising the expected product are combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is taken up in diethyl ether, triturated and then filtered. The solid is dried in a desiccator under reduced pressure (2 Pa) at a temperature in the region of 35° C. and then redissolved in 70 cm3 of ethyl acetate and treated with 50 cm3 of aqueous 1N sodium hydroxide solution. After separation of the phases by settling, the organic phase is washed with 50 cm3 of aqueous 1N sodium hydroxide solution. The aqueous extracts are combined and then treated with aqueous 5N hydrochloric acid solution to pH 1. After extraction with 3 times 50 cm3 of ethyl acetate, the organic extracts are combined, washed with 100 cm3 of saturated brine, dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 0.36 g of (5,6-dichloro-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetic acid is thus obtained in the form of a yellow solid. (Rf=0.33, thin layer chromatography on silica gel, eluent: dichloromethane/methanol (90/10 by volume)).

Workup

  1. stirringThe reaction mixture is stirred at a temperature in the region of 20° C. for 18 hours
  2. concentrationis then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  3. additionThe residue is taken up in a mixture of 5 cm3 of water and 15 cm3 of diethyl ether
  4. stirringis then stirred at a temperature in the region of 20° C. for 1 hour
  5. concentrationThe mixture is concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  6. additionThe residue is taken up in a mixture of dichloromethane and ethyl acetate
  7. filtrationfiltered
  8. customThe filtrate is purified by chromatography under argon pressure (80 kPa)
  9. washon a cartridge of silica gel (particle size 32-63 μm), eluting with a mixture of dichloromethane/methanol (95/5 by volume)
  10. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  11. customtriturated
  12. filtrationfiltered
  13. customThe solid is dried in a desiccator under reduced pressure (2 Pa) at a temperature in the region of 35° C.
  14. dissolutionredissolved in 70 cm3 of ethyl acetate
  15. additiontreated with 50 cm3 of aqueous 1N sodium hydroxide solution
  16. customAfter separation of the phases
  17. washthe organic phase is washed with 50 cm3 of aqueous 1N sodium hydroxide solution
  18. additiontreated with aqueous 5N hydrochloric acid solution to pH 1
  19. extractionAfter extraction with 3 times 50 cm3 of ethyl acetate
  20. washwashed with 100 cm3 of saturated brine
  21. dry with materialdried over magnesium sulfate
  22. filtrationfiltered
  23. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-af678b5efe58447c88a6664b799ce1e3
Source dataset
uspto-grants-2009_09
Patent number
US07589117B2

Reaction notes

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