L-Glutamine → N2-((9H-Fluoren-9-ylmethoxy)carbonyl)-L-glutamine

HRID 620912Notes

Reaction equation

HRID 620912 reaction equation
[NH2:1][C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][C:5](=[O:7])[NH2:6].[CH:11]1[C:23]2[CH:22]([CH2:24][O:25][C:26](Cl)=[O:27])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]=2[CH:14]=[CH:13][CH:12]=1.C(N(C(C)C)CC)(C)C>>[NH:1]([C:26]([O:25][CH2:24][CH:22]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]2[C:23]1=[CH:11][CH:12]=[CH:13][CH:14]=2)=[O:27])[C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][C:5](=[O:7])[NH2:6]

Participants

4

Reactant 3

HCID 5961L-GlutamineHCID 343679-Fluorenylmethyl chloroformateHCID 81531Diisopropylethylamine

Product 1

HCID 2724775N2-((9H-Fluoren-9-ylmethoxy)carbonyl)-L-glutamine

Procedure

5.48 g (37.5 mmoles) of finely ground glutamine (Chemical Dynamics Corp.) was placed in a 250 mL round bottom flask (oven dried) which was fitted with a heating mantle and condenser (oven dried). A nitrogen gas line was attached at the top of the condenser. The solid was suspended in 87.5 mL of dry N,N-dimethyl-acetamide and stirred vigorously. 19.04 mL (150 mmoles) of Tms-Cl was injected in one portion. The mixture was warmed slightly for 1 hour and cooled in an ice bath. 9-Fluorenylmethyloxycarbonyl chloride (6.47 g, 25 mmoles) and 19.78 mL (175 mmoles) of diisopropylethylamine were added. The solution was stirred in ice for 20 minutes and warmed to room temperature for 1-1.5 hrs. The mixture was concentrated on a rotary evaporator and then distributed between 200 mL diethyl ether and 250 mL 2.5% sodium bicarbonate. The phases were separated and the aqueous layer was extracted with 2×50 mL diethyl ether. The ether layers were backwashed with 2×25 mL H2O. The combined aqueous layers were acidified to pH 2 with 1.0N HCl. The white precipitate was filtered, washed with cold H2O and dried under high vacuum. Appropriate solvents were used to recrystallize the product. The product was found to be homogeneous (Table II).

Workup

  1. custom(oven dried) which
  2. customwas fitted with a heating mantle and condenser (oven dried)
  3. temperatureThe mixture was warmed slightly for 1 hour
  4. temperaturecooled in an ice bath
  5. stirringThe solution was stirred in ice for 20 minutes
  6. concentrationThe mixture was concentrated on a rotary evaporator
  7. customThe phases were separated
  8. extractionthe aqueous layer was extracted with 2×50 mL diethyl ether
  9. filtrationThe white precipitate was filtered
  10. washwashed with cold H2O
  11. customdried under high vacuum
  12. customto recrystallize the product

Sources & evidence

ORD record
ord-2e21bb2e1c1948fbacea004f6b2f0886
Source dataset
uspto-grants-1989_04
Patent number
US04822890

Reaction notes

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