HCID 70045307, compound → HCID 86748804, compound

HRID 1648119Notes

Reaction equation

HRID 1648119 reaction equation
[C:1]1([CH2:7][CH2:8][C:9]([NH:11][C@H:12]([C:16]([NH:18][C@H:19]([C:21]([NH:23][CH:24]2[CH:28]([O:29]CC3C=CC=CC=3)[O:27][C:26](=[O:37])[CH2:25]2)=[O:22])[CH3:20])=[O:17])[CH:13]([CH3:15])[CH3:14])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>CN(C)C=O.CO.[OH-].[OH-].[Pd+2]>[C:1]1([CH2:7][CH2:8][C:9]([NH:11][C@H:12]([C:16]([NH:18][C@H:19]([C:21]([NH:23][CH:24]([CH:28]=[O:29])[CH2:25][C:26]([OH:37])=[O:27])=[O:22])[CH3:20])=[O:17])[CH:13]([CH3:14])[CH3:15])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 1

HCID 70045307HCID 70045307, compound

Product 1

HCID 86748804HCID 86748804, compoundYield 72.4%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 188 mg of N-(3-phenylpropionyl-valinyl-alaninyl)-4-amino-5-benzyloxy-2-oxo-tetrahydrofuran in 2 mL of dimethylformamide and 3 mL of methanol was added ~100 mg of Pd(OH)2 on carbon. After the mixture had been stirred vigorously under hydrogen for 3 hours, the mixture was filtered through a 0.22 μm nylon membrane filter and concentrated. The residue was purified by MPLC on silica-gel (22×300 mm column, eluted with a gradient of dichloromethane to 8% formic acid and 32% methanol in dichloromethane) to afford 112 mg of the title compound as a colorless solid: 1H NMR (400 MHz, CD3OD (1:1 mixture of diastereomeric hemiacetals in this solvent)) δ7.3-7.1 (m, 5H, Ar--H), 4.58 (d, 0.5H, J=4.06 Hz, CH(OH)(OCD3)), 4.56 (d, 0.5H, J=3.96 Hz, CH(OH)(OCD3)), 4.34 (m, 1H, CHN), 4.24 (m, 1H, CHN), 4.02 (d, 1H, J=7.38 Hz, CHN), 2.91 (t, 2H, J=7.61Hz, CH2CON), 2.7-2.4 (m, 4H, CH2Ph, CH2CO2), 2.00 (m, 1H, CH(CH3)2), 1.32 (d, 3H, J=7.10 Hz, CHCH3), 0.88 (d, 3H, J=6.82 Hz, CH(CH3)2), 0.85 (d, 3H, J=6.83 Hz, CH(CH3)2).

Workup

  1. filtrationthe mixture was filtered through a 0.22 μm nylon membrane
  2. filtrationfilter
  3. concentrationconcentrated
  4. customThe residue was purified by MPLC on silica-gel (22×300 mm column
  5. washeluted with a gradient of dichloromethane to 8% formic acid and 32% methanol in dichloromethane)

Sources & evidence

ORD record
ord-99db36752f0a41259a84438becaf4eb0
Source dataset
uspto-grants-1995_07
Patent number
US05434248

Reaction notes

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