Anisole → D-Cysteinyl-L-proline acetate

HRID 261322Notes

Reaction equation

HRID 261322 reaction equation
C([O:5][C:6](=[O:34])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[C:12](=[O:33])[C@@H:13]([CH2:22][S:23]CC1C=CC(OC)=CC=1)[NH:14]C(OC(C)(C)C)=O)(C)(C)C.C1(OC)C=CC=CC=1.FC(F)(F)S(O)(=O)=O>ClCCl>[C:6]([OH:34])(=[O:5])[CH3:7].[NH2:14][C@@H:13]([C:12]([N:8]1[CH2:9][CH2:10][CH2:11][C@H:7]1[C:6]([OH:34])=[O:5])=[O:33])[CH2:22][SH:23]

Participants

5

Reactant 3

HCID 7519AnisoleHCID 62406Trifluoromethanesulfonic acidHCID 22805345N-tert-butyloxycarbonyl-S-p-methoxybenzyl-D-cysteinyl-L-proline tert-butyl ester

Product 1

HCID 86736006D-Cysteinyl-L-proline acetate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N-tert-butyloxycarbonyl-S-p-methoxybenzyl-D-cysteinyl-L-proline tert-butyl ester (1.8 g) and anisole (4.4 ml) in dichloromethane (8 ml) chilled in an ice bath, trifluoromethane sulfonic acid (6.0 g) is added. The ice bath is removed and the mixture is stirred at room temperature for thirty minutes. The dichloromethane is removed in vacuo and the residue is triturated with hexane (2×200 ml). The residue is dissolved in water and extracted twice with ether. The aqueous phase is applied to a column of 200 ml of cation exchange resin [Dowex 50] in the hydrogen cycle. The column is washed with water until no more acidic material is eluted. The D-cysteinyl-L-proline acetate is eluted with a pyridine-acetic acid buffer pH 6.5, yield 0.66 g. Rf =0.38 (silica gel, chloroform:methanol:acetic acid:water).

Workup

  1. customThe ice bath is removed
  2. customThe dichloromethane is removed in vacuo
  3. customthe residue is triturated with hexane (2×200 ml)
  4. dissolutionThe residue is dissolved in water
  5. extractionextracted twice with ether
  6. washThe column is washed with water until no more acidic material
  7. washis eluted
  8. washThe D-cysteinyl-L-proline acetate is eluted with a pyridine-acetic acid buffer pH 6.5, yield 0.66 g

Sources & evidence

ORD record
ord-efbf41f7e1934847bbb6da7b1f267a21
Source dataset
uspto-grants-1979_08
Patent number
US04165320

Reaction notes

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