Sulfuric Acid → (2S)-2-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)-4-[(triphenylmethyl)carbamoyl]butanoic acid

HRID 1110194Notes

Reaction equation

HRID 1110194 reaction equation
[NH:1]([C:11]([O:13][CH2:14][CH:15]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]2[C:16]1=[CH:17][CH:18]=[CH:19][CH:20]=2)=[O:12])[C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][C:5](=[O:7])[NH2:6].[C:28]1([C:34]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.S(=O)(=O)(O)O.C(OC(=O)C)(=O)C>C(O)(=O)C>[NH:1]([C:11]([O:13][CH2:14][CH:15]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]2[C:16]1=[CH:17][CH:18]=[CH:19][CH:20]=2)=[O:12])[C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][C:5](=[O:7])[NH:6][C:34]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)([C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1)[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 6457TriphenylcarbinolHCID 7918Acetic AnhydrideHCID 2724775N2-((9H-Fluoren-9-ylmethoxy)carbonyl)-L-glutamine

Product 1

HCID 10919157(2S)-2-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)-4-[(triphenylmethyl)carbamoyl]butanoic acid

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 7.4 g of Fmoc-Gln-OH (20 mmol) and 10.4 g of triphenylmethanol (40 mmol) in 300 ml of acetic acid is stirred at 100° for 10 minutes. Addition of 0.1 ml of conc. sulfuric acid is followed by stirring at 100° for a further 15 minutes to produce a clear yellow solution. This is evaporated at 60° under reduced pressure, and the residue is then dried under reduced pressure for 10 minutes. The solid residue is dissolved in 60 ml of acetic acid at 60°, left at 60° for 20 minutes, then 2 ml of acetic anhydride (20 mmol) are added, and after 1 hour at 60°, the mixture is evaporated under reduced pressure. The oily residue is dried at 60° for 10 minutes, then dissolved in 100 ml of acetic acid and added dropwise to 500 ml of ice-cold water. The precipitate is filtered off, thoroughly washed with water and dissolved in ethyl acetate; the aqueous phase is separated off, and the organic phase is washed with a saturated aqueous sodium chloride solution. The organic solution is dried over sodium sulfate and then evaporated to dryness, and the residue is dissolved in 50 ml of 1,2-dichloroethane and applied to 100 g of silica gel; elution is with 1,2-dichloroethane and 1,2-dichloroethane containing 2%, then 4% methanol. The fractions containing Fmoc-Gln(Trt)-OH are evaporated under reduced pressure, and the product is crystallized from a mixture of ethyl acetate and diisopropyl ether, m.p. above 125°.

Workup

  1. stirringby stirring at 100° for a further 15 minutes
  2. customto produce a clear yellow solution
  3. customThis is evaporated at 60° under reduced pressure
  4. customthe residue is then dried under reduced pressure for 10 minutes
  5. dissolutionThe solid residue is dissolved in 60 ml of acetic acid at 60°
  6. waitleft at 60° for 20 minutes
  7. waitafter 1 hour at 60°
  8. customthe mixture is evaporated under reduced pressure
  9. customThe oily residue is dried at 60° for 10 minutes
  10. dissolutiondissolved in 100 ml of acetic acid
  11. additionadded dropwise to 500 ml of ice-cold water
  12. filtrationThe precipitate is filtered off
  13. washthoroughly washed with water
  14. dissolutiondissolved in ethyl acetate
  15. customthe aqueous phase is separated off
  16. washthe organic phase is washed with a saturated aqueous sodium chloride solution
  17. dry with materialThe organic solution is dried over sodium sulfate
  18. customevaporated to dryness
  19. dissolutionthe residue is dissolved in 50 ml of 1,2-dichloroethane
  20. washelution
  21. additionThe fractions containing Fmoc-Gln(Trt)-OH
  22. customare evaporated under reduced pressure
  23. customthe product is crystallized from a mixture of ethyl acetate and diisopropyl ether, m.p. above 125°

Sources & evidence

ORD record
ord-65db3d4e9f8e4065883a42574e248f4d
Source dataset
uspto-grants-1994_06
Patent number
US05324833

Reaction notes

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