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

HRID 1707727Notes

Reaction equation

HRID 1707727 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. After the addition of 0.1 ml of concentrated sulfuric acid the whole is stirred at 100° for a further 15 minutes, a clear yellow solution forming. This is concentrated by evaporation under reduced pressure at 60°, and the residue is 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 whole is concentrated by evaporation under reduced pressure. The oily residue is dried for 10 minutes at 60°, then dissolved in 100 ml of acetic acid and introduced dropwise into 500 ml of ice-cold water. The precipitate is isolated by filtration, washed well 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. After drying over sodium sulfate, the organic solution is concentrated to dryness by evaporation, the residue is dissolved in 50 ml of 1,2-dichloroethane and applied to 100 g of silica gel; elution is carried out with 1,2-dichloroethane and with 1,2-dichloroethane containing 2%, then 4%, methanol. The fractions containing the Fmoc-Gln(Trt)-OH are concentrated by evaporation under reduced pressure, and the product is crystallised from a mixture of ethyl acetate and diisopropyl ether, m.p. from 125°.

Workup

  1. stirringis stirred at 100° for a further 15 minutes
  2. customa clear yellow solution forming
  3. concentrationThis is concentrated by evaporation under reduced pressure at 60°
  4. customthe residue is 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. concentrationis concentrated by evaporation under reduced pressure
  8. customThe oily residue is dried for 10 minutes at 60°
  9. dissolutiondissolved in 100 ml of acetic acid
  10. additionintroduced dropwise into 500 ml of ice-cold water
  11. customThe precipitate is isolated by filtration
  12. washwashed well with water
  13. dissolutiondissolved in ethyl acetate
  14. customthe aqueous phase is separated off
  15. washthe organic phase is washed with a saturated aqueous sodium chloride solution
  16. dry with materialAfter drying over sodium sulfate
  17. concentrationthe organic solution is concentrated to dryness by evaporation
  18. dissolutionthe residue is dissolved in 50 ml of 1,2-dichloroethane
  19. washelution
  20. additionThe fractions containing the Fmoc-Gln(Trt)-OH
  21. concentrationare concentrated by evaporation under reduced pressure
  22. customthe product is crystallised from a mixture of ethyl acetate and diisopropyl ether
  23. customm.p. from 125°

Sources & evidence

ORD record
ord-f11b7bc260164e6bbd8fe6fa3d872868
Source dataset
uspto-grants-1994_10
Patent number
US05354843

Reaction notes

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