Trifluoroacetic acid → 2,6-Dimethyl-L-tyrosyl-N-[(2S)-2-amino-3-phenylpropyl]-D-alaninamide

HRID 1849985

Reaction equation

HRID 1849985 reaction equation
C(OC([NH:8][C@H:9]([C:20]([NH:22][C@@H:23]([C:25]([NH:27][CH2:28][C@@H:29]([NH:37]C(OC(C)(C)C)=O)[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:26])[CH3:24])=[O:21])[CH2:10][C:11]1[C:16]([CH3:17])=[CH:15][C:14]([OH:18])=[CH:13][C:12]=1[CH3:19])=O)(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl.CO>[CH3:19][C:12]1[CH:13]=[C:14]([OH:18])[CH:15]=[C:16]([CH3:17])[C:11]=1[CH2:10][C@@H:9]([C:20]([NH:22][C@@H:23]([C:25]([NH:27][CH2:28][C@@H:29]([NH2:37])[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:26])[CH3:24])=[O:21])[NH2:8]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71229494N-(tert-butoxycarbonyl)-2,6-dimethyl-L-tyrosyl-N-{(2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropyl}-D-alaninamide

Product 1

HCID 712295022,6-Dimethyl-L-tyrosyl-N-[(2S)-2-amino-3-phenylpropyl]-D-alaninamideYield 100%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

N-(tert-butoxycarbonyl)-2,6-dimethyl-L-tyrosyl-N-{(2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropyl}-D-alaninamide (6.1 g, 9.1 mmol) was dissolved in 25 mL dichloromethane and 25 mL TFA and stirred at room temperature for 3 h under a nitrogen atmosphere. The mixture was evaporated under reduced pressure to give a yellow gum. The gum was dissolved in 20 mL methanol and split into 4 equal portions. Each was loaded onto a separate 10 g SCX-2 cartridge, pre-wetted with methanol. Each cartridge was flushed with 50 mL of methanol to remove non-basic impurities, and then with 80 mL of 2N ammonia solution in methanol to elute the desired product. Fractions containing product were concentrated in vacuo to give a pale yellow gum. This was heated with a hot air gun and placed under vacuum (15 mm Hg) overnight to give 3.7 g (100%) of the title compound as a stiff white foam.

Workup

  1. customThe mixture was evaporated under reduced pressure
  2. customto give a yellow gum
  3. customsplit into 4 equal portions
  4. customEach cartridge was flushed with 50 mL of methanol
  5. customto remove non-basic impurities
  6. washwith 80 mL of 2N ammonia solution in methanol to elute the desired product
  7. additionFractions containing product
  8. concentrationwere concentrated in vacuo
  9. customto give a pale yellow gum
  10. temperatureThis was heated with a hot air gun
  11. customplaced under vacuum (15 mm Hg) overnight

Sources & evidence

ORD record
ord-53c6770ba37647e68b58f1df39d81b24
Source dataset
uspto-grants-2015_02
Patent number
US08957025B2

Linked notes

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