benzyl (2S)-2-[[(2S)-3-(difluoromethoxy)-2-[(2-morpholinoacetyl)amino]propanoyl]amino]-3-phenyl-propanoate → (2S)-2-[[(2S)-3-(difluoromethoxy)-2-[(2-morpholinoacetyl)-amino]propanoyl]amino]-3-phenyl-propanoic acid

HRID 61304Notes

Reaction equation

HRID 61304 reaction equation
[F:1][CH:2]([F:37])[O:3][CH2:4][C@H:5]([NH:27][C:28](=[O:36])[CH2:29][N:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1)[C:6]([NH:8][C@@H:9]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:10]([O:12]CC1C=CC=CC=1)=[O:11])=[O:7]>C1COCC1.[Pd]>[F:37][CH:2]([F:1])[O:3][CH2:4][C@H:5]([NH:27][C:28](=[O:36])[CH2:29][N:30]1[CH2:31][CH2:32][O:33][CH2:34][CH2:35]1)[C:6]([NH:8][C@@H:9]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:10]([OH:12])=[O:11])=[O:7]

Participants

4

Reactant 1

HCID 118247689benzyl (2S)-2-[[(2S)-3-(difluoromethoxy)-2-[(2-morpholinoacetyl)amino]propanoyl]amino]-3-phenyl-propanoate

Product 1

HCID 90040787(2S)-2-[[(2S)-3-(difluoromethoxy)-2-[(2-morpholinoacetyl)-amino]propanoyl]amino]-3-phenyl-propanoic acid

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of benzyl (2S)-2-[[(2S)-3-(difluoromethoxy)-2-[(2-morpholinoacetyl)amino]propanoyl]amino]-3-phenyl-propanoate (1.54 g, 2.96 mmol) in THF (10 mL) was treated with palladium (10 wt. % on activated carbon) (157 mg, 0.148 mmol) and stirred under an atmosphere of hydrogen, balloon pressure, for 1 h. The mixture was then filtered through a pad of Celite™ and concentrated in vacuo giving the compound of Formula XVIII(a) (1.27 g, quantitative yield) as colourless foam. 1H NMR (CDCl3, 400 MHz): δ (ppm) 8.09 (m, 1H), 7.24-7.05 (m, 5H), 6.10 (t, J=74 Hz, 1H), 5.6 (brs, 1H), 4.70-4.60 (m, 2H), 4.15-4.01 (m, 1H), 3.95-3.85 (m, 1H), 3.70-3.55 (m, 4H), 3.25-2.90 (m, 4H), 2.65-2.50 (m, 4H).

Workup

  1. filtrationThe mixture was then filtered through a pad of Celite™
  2. concentrationconcentrated in vacuo
  3. customgiving the compound of Formula XVIII(a) (1.27 g, quantitative yield) as colourless foam

Sources & evidence

ORD record
ord-ff6efaeae2c44fe2aa49f00ff9a4ff03
Source dataset
uspto-grants-2016_09
Patent number
US09441012B2

Reaction notes

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