Water → HCID 86756336, compound

HRID 567944Notes

Reaction equation

HRID 567944 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][C@@H:16]([C:22]([NH:24][CH2:25][C@@H:26]([C:56]([O:58]C(C)(C)C)=[O:57])[CH2:27][C:28]1([C:33]([NH:35][C@H:36]([C:49]([O:51]C(C)(C)C)=[O:50])[CH2:37][C:38]2[CH:43]=[CH:42][C:41]([O:44]C(C)(C)C)=[CH:40][CH:39]=2)=[O:34])[CH2:32][CH2:31][CH2:30][CH2:29]1)=[O:23])[NH:17][S:18]([CH3:21])(=[O:20])=[O:19])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O.O>ClCCl.C(OCC)(=O)C>[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][C@@H:16]([C:22]([NH:24][CH2:25][C@@H:26]([C:56]([OH:58])=[O:57])[CH2:27][C:28]1([C:33]([NH:35][C@H:36]([C:49]([OH:51])=[O:50])[CH2:37][C:38]2[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=2)=[O:34])[CH2:32][CH2:31][CH2:30][CH2:29]1)=[O:23])[NH:17][S:18]([CH3:21])(=[O:20])=[O:19])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 86756335HCID 86756335, compound

Product 1

HCID 86756336HCID 86756336, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
35 °C

Procedure

Tert-butyl (S,S,S)-N-(1-[3-(N6-benzyloxycarbonyl-N2-mesyllysylamino)-2-(tert-butoxycarbonyl)propyl]-1-cyclopentylcarbonyl)-O4-tert-butyltyrosinate (404 g) was dissolved in dichloromethane (810 ml). Anisole (769 g) was added in one portion and then trifluoroacetic acid (1.158 kg) added dropwise over approximately 10 minutes. On completion of the addition, the reaction was stirred at 35° C. for 6 hours and then stirred at room temperature overnight. Water (1000 ml) was added and three layers formed. The top and bottom layers were combined, dissolved in ethyl acetate (2 l) and the resulting solution washed with brine. The organic phase was mixed with brine, the pH adjusted to 3 and the layers allowed to separate. Three layers formed. The organic phases were separated, taken up in ethyl acetate and extracted with saturated aqueous sodium bicarbonate (1.6 l) solution and brine (0.5 l). The combined aqueous layers were washed with ethyl acetate, then acidified and extracted with ethyl acetate to give an ethyl acetate solution (1.54 l) of the title compound. This solution was either used directly (e.g. see Example 1) or the solvent removed to provide the title compound.

Workup

  1. additionOn completion of the addition
  2. stirringstirred at room temperature overnight
  3. customthree layers formed
  4. washthe resulting solution washed with brine
  5. additionThe organic phase was mixed with brine
  6. customto separate
  7. customThree layers formed
  8. customThe organic phases were separated
  9. extractionextracted with saturated aqueous sodium bicarbonate (1.6 l) solution and brine (0.5 l)
  10. washThe combined aqueous layers were washed with ethyl acetate
  11. extractionextracted with ethyl acetate

Sources & evidence

ORD record
ord-38332fbfa447458f9f59438fa36b02d4
Source dataset
uspto-grants-2001_01
Patent number
US06180665B2

Reaction notes

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