(E)-benzyl 3-(((3S,6S,7R,8S)-8-benzyl-3-((tert-butoxycarbonyl)amino)-6-methyl-4-oxo-1,5-dioxonan-7-yl)oxy)acrylate → 3-(((3S,6S,7R,8S)-8-benzyl-3-((tert-butoxycarbonyl)amino)-6-methyl-4-oxo-1,5-dioxonan-7-yl)oxy)propanoic acid

HRID 75747Notes

Reaction equation

HRID 75747 reaction equation
[CH2:1]([C@H:8]1[CH2:16][O:15][CH2:14][C@H:13]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:12](=[O:25])[O:11][C@@H:10]([CH3:26])[C@@H:9]1[O:27]/[CH:28]=[CH:29]/[C:30]([O:32]CC1C=CC=CC=1)=[O:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>CCOC(C)=O.[Pd]>[CH2:1]([C@H:8]1[CH2:16][O:15][CH2:14][C@H:13]([NH:17][C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19])[C:12](=[O:25])[O:11][C@@H:10]([CH3:26])[C@@H:9]1[O:27][CH2:28][CH2:29][C:30]([OH:32])=[O:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 1

HCID 86701240(E)-benzyl 3-(((3S,6S,7R,8S)-8-benzyl-3-((tert-butoxycarbonyl)amino)-6-methyl-4-oxo-1,5-dioxonan-7-yl)oxy)acrylate

Product 1

HCID 867012393-(((3S,6S,7R,8S)-8-benzyl-3-((tert-butoxycarbonyl)amino)-6-methyl-4-oxo-1,5-dioxonan-7-yl)oxy)propanoic acidYield 104%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of (E)-benzyl 3-(((3S,6S,7R,8S)-8-benzyl-3-((tert-butoxycarbonyl)amino)-6-methyl-4-oxo-1,5-dioxonan-7-yl)oxy)acrylate (490 mg, 0.908 mmol, 1.00 equiv) and 10% Pd/C (48 mg, 0.045 mmol, 0.05 equiv) in EtOAc (9.1 mL, 0.1 M) was stirred for 16 h under an atmosphere of H2 (1 atm, balloon pressure) at room temperature. The reaction mixture was filtered through a plug of Celite® and the plug was washed with EtOAc (50 mL). The filtrate was concentrated to provide a white solid that was shown to be a mixture of partially reduced products by 1H NMR. This material was resubjected to the reaction conditions and isolated as before to provide 3-(((3S,6S,7R,8S)-8-benzyl-3-((tert-butoxycarbonyl)amino)-6-methyl-4-oxo-1,5-dioxonan-7-yl)oxy)propanoic acid (425 mg, 104%) as a white solid, contaminated with a small amount of EtOAc: IR (ATR) 3319, 2977, 2930, 2879, 1710, 1497, 1391, 1368, 1246, 1201, 1161, 1065, 851, 750 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.31-7.22 (m, 2H), 7.22-7.12 (m, 3H), 5.14 (d, J=8.2 Hz, 1H), 4.93 (dq, J=9.0, 6.4 Hz, 1H), 4.59 (dd, J=15.2, 7.4 Hz, 1H), 3.99-3.84 (m, 2H), 3.79 (dt, J=8.9, 6.1 Hz, 1H), 3.48-3.31 (m, 2H), 3.24 (dd, J=11.2, 7.5 Hz, 1H), 3.16 (t, J=9.0 Hz, 1H), 3.12-3.06 (m, 1H), 2.60 (t, J=6.1 Hz, 2H), 2.32 (t, J=12.6 Hz, 1H), 1.90 (s, 1H), 1.48 (d, J=6.4 Hz, 3H), 1.42 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 176.37, 172.28, 154.99, 139.74, 129.16, 128.42, 126.13, 85.30, 80.17, 75.27, 72.78, 72.16, 67.35, 52.88, 47.20, 35.09, 28.27, 18.71; HRMS-ESI (m/z) [M+Na]+ calc'd for C23H33NO8Na, 474.2098. found, 474.2118.

Workup

  1. filtrationThe reaction mixture was filtered through a plug of Celite®
  2. washthe plug was washed with EtOAc (50 mL)
  3. concentrationThe filtrate was concentrated
  4. customto provide a white solid
  5. additiona mixture of partially reduced products by 1H NMR
  6. customThis material was resubjected to the reaction conditions
  7. customisolated as before

Sources & evidence

ORD record
ord-35066a6a9a0b4b1f84981646fac6df54
Source dataset
uspto-grants-2014_09
Patent number
US08835462B2

Reaction notes

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