4-Methylmorpholine → L-Glutamine, N2-((1,1-dimethylethoxy)carbonyl)-

HRID 1709960Notes

Reaction equation

HRID 1709960 reaction equation
[NH:1]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][C:5](=[O:7])[NH2:6].[NH2:18][C:19]1[CH:28]=[C:27]2[C:22]([C:23]([CH3:30])=[CH:24][C:25](=[O:29])[O:26]2)=[CH:21][CH:20]=1.CN1CCOCC1.ClC(OCC(C)C)=O>CN(C=O)C>[NH:1]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][C:5](=[O:7])[NH2:6].[NH:1]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C@H:2]([C:8]([NH:18][C:19]1[CH:28]=[C:27]2[C:22]([C:23]([CH3:30])=[CH:24][C:25](=[O:29])[O:26]2)=[CH:21][CH:20]=1)=[O:10])[CH2:3][CH2:4][C:5](=[O:7])[NH2:6]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 83687L-Glutamine, N2-((1,1-dimethylethoxy)carbonyl)-2×HCID 922497-Amino-4-methylcoumarin2×

Product 2

HCID 83687L-Glutamine, N2-((1,1-dimethylethoxy)carbonyl)-HCID 131716515HCID 131716515, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Boc-Gln-AMC was prepared by coupling anhydrous Boc-Gln-OH (7.03 g, 28.5 mmol) to 7-amino-4-methylcoumarin (AMC) by the mixed anhydride coupling procedure outlined above. First, a solution of a mixed anhydride of Boc-Gln-OH was prepared by reacting Boc-Gln-OH with an equivalent of N-methylmorpholine and an equivalent of isobutyl chloroformate, and the resulting solution was added to AMC (5.00 g, 28.5 mmol) dissolved in 30 mL DMF. After the resulting reaction was complete, the reaction mixture was filtered and the filtrate concentrated. Product (5 g) was separated from the filtrate and dissolved in 75 mL hot methanol. This solution was then concentrated to about 30 mL and cooled. Solid AMC was separated from the solution by filtration, and the remaining filtrate was further concentrated to a volume of about 5 mL. This concentrated solution was then diluted with 30 mL chloroform, and the resulting solution applied to a 4 cm column containing about 30 g silica gel. Residual AMC was eluted from the column with additional chloroform, and product Boc-Gln-AMC (0.97 g) was then recovered from the column by elution with 2% methanol in chloroform. Recrystallization of product from methanol provided 0.46 g of purified Boc-Gln-AMC, mp 260.5-207°. TLC with methanol:chloroform (1:9) indicated a single spot, Rf 0.28.

Workup

  1. customBoc-Gln-AMC was prepared
  2. customAfter the resulting reaction
  3. filtrationthe reaction mixture was filtered
  4. concentrationthe filtrate concentrated
  5. customProduct (5 g) was separated from the filtrate
  6. dissolutiondissolved in 75 mL hot methanol
  7. concentrationThis solution was then concentrated to about 30 mL
  8. temperaturecooled
  9. customSolid AMC was separated from the solution by filtration
  10. concentrationthe remaining filtrate was further concentrated to a volume of about 5 mL
  11. additionThis concentrated solution was then diluted with 30 mL chloroform
  12. additioncontaining about 30 g silica gel
  13. washResidual AMC was eluted from the column with additional chloroform, and product Boc-Gln-AMC (0.97 g)
  14. customwas then recovered from the column by elution with 2% methanol in chloroform
  15. customRecrystallization of product from methanol

Sources & evidence

ORD record
ord-ff083fb2098940dabef714e5c0aa207c
Source dataset
uspto-grants-1990_08
Patent number
US04952493

Reaction notes

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