Ethyl 4-amino-N-(tert-butoxycarbonyl)-L-phenylalaninate → HCID 69331402, compound

HRID 507703Notes

Reaction equation

HRID 507703 reaction equation
C(OC(=O)[C@@H](NC(OC(C)(C)C)=O)CC1C=CC(N)=CC=1)C.CO.C(Cl)Cl.[CH2:28]([O:30][C:31](=[O:59])[C@@H:32]([NH:51]C(OC(C)(C)C)=O)[CH2:33][C:34]1[CH:39]=[CH:38][C:37]([NH:40][C:41]2[C:50]3[C:45](=[CH:46][CH:47]=[N:48][CH:49]=3)[CH:44]=[CH:43][N:42]=2)=[CH:36][CH:35]=1)[CH3:29]>C(OC(O)C)C>[NH2:51][C@@H:32]([CH2:33][C:34]1[CH:39]=[CH:38][C:37]([NH:40][C:41]2[C:50]3[C:45](=[CH:46][CH:47]=[N:48][CH:49]=3)[CH:44]=[CH:43][N:42]=2)=[CH:36][CH:35]=1)[C:31]([O:30][CH2:28][CH3:29])=[O:59]

Participants

5

Reactant 3

HCID 10638537Ethyl 4-amino-N-(tert-butoxycarbonyl)-L-phenylalaninateHCID 21226129Dichloromethane methanolHCID 68468681HCID 68468681, compound

Product 1

HCID 69331402HCID 69331402, compound

Reagents, catalysts & solvents 1

HCID 101298981-EthoxyethanolSolvent

Procedure

A solution of ethyl-(S)-3-[4-aminophenyl]-2-[t-butoxycarbonylamino]propanoate (638 mg, 2.07 mmol) and Intermediate 11 (310 mg, 1.88 mmol) in ethoxyethanol (2 ml) was stirred at 120° for 15 min and at 100° for 1 h under nitrogen. The volatiles were removed in vacuo and the dark residue partitioned between EtOAc (70 ml) and saturated aqueous NaHCO3 (10 ml). The phases were separated and the aqueous layer re-extracted with EtOAc (2×30 ml). The combined organic extracts were washed with brine (10 ml)T dried (Na2SO4) and evaporated in vacuo to afford a dark foam. Chromatography (SiO2; 5 to 10% MeOH/DCM) afforded a mixture of ethyl-(S)-3-[4-(2,7-naphthyridin-1-ylamino)phenyl]-2-[(t-butoxycarbonyl)amino]propanoate and some of the title compound (730 mg). This mixture was treated with a solution of trifluoroacetic acid (5 ml) and DCM (5 ml) at room temperature for 1 h. The volatiles were removed in vacuo and the residue partitioned between EtOAc (75 ml) and saturated aqueous NaHCO3 (20 ml). The phases were separated and the aqueous layer re-extracted with EtOAc (3×30 ml). The combined organic extracts were washed with brine (10 ml), dried (Na2SO4) and evaporated in vacuo to afford an orange solid. Chromatography (SiO2; 10% MeOH/DCM) afforded the title compound as a straw-coloured solid (420 mg, 60% over two steps). δH (CDCl3) 10.70 (1H, s), 10.31 (1H, s), 9.44 (1H, d, J 5.6 Hz), 8.94 (1H, d, J 5.6 Hz), 8.55 (1H, d, J 7.3 Hz), 8.54 (2H, d, J 8.5 Hz), 8.46 (1H, d, J 5.6 Hz), 7.94 (2H, d, J 8.5 Hz), 4.84 (2H, q, J 7.1 Hz), 4.35 (1H, t, J 6.6 Hz), 4.10 (2H, br s), 3.64 (1H, dd, J 13.5, 6.4 Hz), 3.56 (1H, dd, J 13.5, 7.0 Hz) and 1.95 (3H, t, J 7.1 Hz); m/z (ES+, 70V) 337 (MH+).

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe dark residue partitioned between EtOAc (70 ml) and saturated aqueous NaHCO3 (10 ml)
  3. customThe phases were separated
  4. extractionthe aqueous layer re-extracted with EtOAc (2×30 ml)
  5. washThe combined organic extracts were washed with brine (10 ml)T
  6. dry with materialdried (Na2SO4)
  7. customevaporated in vacuo
  8. customto afford a dark foam

Sources & evidence

ORD record
ord-79072d5450f04a96a35487a88cd1092c
Source dataset
uspto-grants-2010_08
Patent number
US07786177B2

Reaction notes

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