L-tert-Leucine → N-[3-(9H-Fluoren-9-yl)propionyl]-L-t-leucine

HRID 1089851Notes

Reaction equation

HRID 1089851 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][CH2:15][C:16](O)=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[NH2:19][C@H:20]([C:25]([OH:27])=[O:26])[C:21]([CH3:24])([CH3:23])[CH3:22]>S(Cl)(Cl)=O.C(=O)([O-])[O-].[Na+].[Na+]>[CH:1]1[C:13]2[CH:12]([CH2:14][CH2:15][C:16]([NH:19][C@H:20]([C:25]([OH:27])=[O:26])[C:21]([CH3:24])([CH3:23])[CH3:22])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 2

HCID 164608L-tert-LeucineHCID 135008763-(9H-Fluoren-9-yl)propanoic acid

Product 1

HCID 15045076N-[3-(9H-Fluoren-9-yl)propionyl]-L-t-leucine

Reagents, catalysts & solvents 2

HCID 10340Sodium CarbonateSolventHCID 24386Thionyl ChlorideSolvent

Procedure

A solution of 3-(fluoren-9-yl)propionic acid (2.4 g, 10 mmol) in thionyl chloride was refluxed for two hours. The reaction mixture was cooled down and the solvent was removed in vacuum. A solution of the resulting 3-(fluoren-9-yl)propionic acid chloride was dissolved in dioxane (20 mL) and added into a solution of L-tert-leucine (4 g, 30.5 mmol) in 10% aqueous sodium carbonate (40 mL). The reaction mixture was monitored by quenching an aliquot with methanol than monitor the resulting methyl ester by TLC (10% MeOH in chloroform). After an 1.5 hr water was added and most of the dioxane was removed in vacuum. The aqueous layer was washed with diethyl ether (×3) then was acidified to pH 1 with 10% HCl. The resulting precipitate was purified by a short path chromatography (silica, 5% MeOH in chloroform) to yield 1.5 g (42.1%), mp 79°-83° C.

Workup

  1. temperatureThe reaction mixture was cooled down
  2. customthe solvent was removed in vacuum
  3. dissolutionA solution of the resulting 3-(fluoren-9-yl)propionic acid chloride was dissolved in dioxane (20 mL)
  4. customby quenching an aliquot with methanol than monitor the resulting methyl ester by TLC (10% MeOH in chloroform)
  5. additionAfter an 1.5 hr water was added and most of the dioxane
  6. customwas removed in vacuum
  7. washThe aqueous layer was washed with diethyl ether (×3)
  8. customThe resulting precipitate was purified by a short path chromatography (silica, 5% MeOH in chloroform)
  9. customto yield 1.5 g (42.1%), mp 79°-83° C.

Sources & evidence

ORD record
ord-70311f986d8f4991afac50a2839d0d89
Source dataset
uspto-grants-1992_01
Patent number
US05079260

Reaction notes

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