Trifluoroacetic acid → D-tryptophanyl-trans-2,5-dicarbethoxypyrrolidine

HRID 1077673Notes

Reaction equation

HRID 1077673 reaction equation
C(O)(C(F)(F)F)=O.CC(OC([NH:15][C@@H:16]([C:27]([OH:29])=O)[CH2:17][C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[NH:20][CH:19]=1)=O)(C)C.[C:30]([C@H:35]1[CH2:39][CH2:38][C@H:37]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[NH:36]1)([O:32][CH2:33][CH3:34])=[O:31].C1(OC)C=CC=CC=1.C1C=C2C(C(O)(O)C(=O)C2=CC=1)=O.C(N(C(C)C)CC)(C)C>C(Cl)Cl.C(Cl)(Cl)Cl.CO>[NH2:15][C@@H:16]([C:27]([N:36]1[C@@H:37]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:38][CH2:39][C@@H:35]1[C:30]([O:32][CH2:33][CH3:34])=[O:31])=[O:29])[CH2:17][C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[NH:20][CH:19]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acid2×HCID 7519AnisoleHCID 10236NinhydrinHCID 81531DiisopropylethylamineHCID 131719485boc-D-Trp (+/-) trans-2,5-dicarbethoxypyrrolidine

Product 1

HCID 67768514D-tryptophanyl-trans-2,5-dicarbethoxypyrrolidineYield 115.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21584188Chloroform methanolSolvent2×

Conditions

Temperature
0 °C

Procedure

A 25% solution of TFA in CH2Cl2 (25 ml) was added at 0° C. to an isomeric mixture 0.94 g (1.9 mmol) of the tryptophan pyrrolidine diester (2) and 0.41 (3.8 mmol) anisole. The reaction mixture was stirred at 0° C. for 15 min and then at room temperature for 2. hr. TLC analysis (93:7, CHCl3 /MeOH) using a ninhydrin indicator showed the complete disappearance of the starting material and the appearance of a new spot near the baseline. Without isolation of this material, the TFA was neutralized by the addition of 12.12 ml of diisopropylethylamine and the mixture turned from dark red to yellow. After stirring at room temperature for approximately six hours, TLC analysis of the reaction mixture (95:5;CHCl3 /MeOH) showed the presence of two major isomers in approximately a 2:1 ratio. After removal of the CH2Cl2 in vacuo, the suspension was extracted into ethyl acetate and washed and dried over anhydrous MgSO4. Concentration in vacuo resulted in 0.88 g of a dark brown oil. Column chromatography over silica gel (CHCl3) produced 0.30g (44%) of the trans isomer that yielded the following 1H NMR (CDCl3, 360 MHz) data:

Workup

  1. customat room temperature
  2. stirringAfter stirring at room temperature for approximately six hours
  3. customAfter removal of the CH2Cl2 in vacuo
  4. extractionthe suspension was extracted into ethyl acetate
  5. washwashed
  6. dry with materialdried over anhydrous MgSO4
  7. concentrationConcentration in vacuo

Sources & evidence

ORD record
ord-ff2ca57b395d4a658b16e80203bdc87a
Source dataset
uspto-grants-1996_08
Patent number
US05543521

Reaction notes

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