(S)-2-((S)-1-tert-butoxycarbonyl-ethylamino)-3-(2',5'-dichloro-biphenyl-4-yl)-propionic acid benzyl ester → (S)-2-((S)-1-tert-butoxycarbonyl-ethylamino)-3-(2',5'-dichloro-biphenyl-4-yl)-propionic acid

HRID 238915Notes

Reaction equation

HRID 238915 reaction equation
C([O:8][C:9](=[O:36])[C@@H:10]([NH:26][C@H:27]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH3:28])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=2[Cl:25])=[CH:14][CH:13]=1)C1C=CC=CC=1>CCOC(C)=O.CO.[Pd]>[C:32]([O:31][C:29]([C@@H:27]([NH:26][C@@H:10]([CH2:11][C:12]1[CH:13]=[CH:14][C:15]([C:18]2[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=2[Cl:25])=[CH:16][CH:17]=1)[C:9]([OH:36])=[O:8])[CH3:28])=[O:30])([CH3:33])([CH3:34])[CH3:35]

Participants

5

Reactant 1

HCID 58280524(S)-2-((S)-1-tert-butoxycarbonyl-ethylamino)-3-(2',5'-dichloro-biphenyl-4-yl)-propionic acid benzyl ester

Product 1

HCID 58280551(S)-2-((S)-1-tert-butoxycarbonyl-ethylamino)-3-(2',5'-dichloro-biphenyl-4-yl)-propionic acidYield 90.8%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

Step 4′: A suspension of (S)-2-((S)-1-tert-Butoxycarbonyl-ethylamino)-3-(2′,5′-dichloro-biphenyl-4-yl)-propionic acid benzyl ester (580 mg, 1.10 mmol) and 5% Pd on carbon (0.146 g) in EtOAc (10 mL) was treated with H2 (balloon) and stirred at rt for 1.5 hour. The resulted precipitate was dissolved in methanol and filtered through celite pad. The filtrate was concentrated under reduced pressure and the obtained residue was re-crystallized from EtOAc to give (S)-2-((S)-1-tert-butoxycarbonyl-ethylamino)-3-(2′,5′-dichloro-biphenyl-4-yl)-propionic acid (438 mg). 1H NMR (400 MHz, DMSO-d6) δ 1.12 (d, 3H, J=7.1 Hz), 1.35 (s, 9H), 2.84 (dd, 2H, J=7.3, 13.6 Hz), 2.95 (dd, 2H, J=6.1, 13.6 Hz), 3.20 (dd, 1H, J=6.8, 13.6 Hz), 3.48 (dd, 1H, J=6.1, 7.3 Hz), 7.33 (d, 2H, J=8.6 Hz), 7.37 (d, 2H, J=8.3 Hz), 7.42-7.49 (m, 2H), 7.60 (d, 2H, J=8.6 Hz); MS: m/z (MH+) 438.

Workup

  1. additionwas treated with H2 (balloon)
  2. filtrationfiltered through celite pad
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customthe obtained residue was re-crystallized from EtOAc

Sources & evidence

ORD record
ord-f709c6f1191e47b8990798be515769ed
Source dataset
uspto-grants-2014_02
Patent number
US08642635B2

Reaction notes

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