HCID 10863544, compound → HCID 86701273, compound

HRID 2276074Notes

Reaction equation

HRID 2276074 reaction equation
[C:1]([O:6][C@@H:7]1[C@@H:15]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:14](=[O:23])[O:13][CH2:12][C@H:11]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C:10](=[O:32])[O:9][C@H:8]1[CH3:33])(=[O:5])[CH:2]([CH3:4])[CH3:3]>C1COCC1.[Rh]>[C:1]([O:6][C@@H:7]1[C@@H:15]([CH2:16][CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[C:14](=[O:23])[O:13][CH2:12][C@H:11]([NH:24][C:25]([O:27][C:28]([CH3:29])([CH3:31])[CH3:30])=[O:26])[C:10](=[O:32])[O:9][C@H:8]1[CH3:33])(=[O:5])[CH:2]([CH3:3])[CH3:4]

Participants

4

Reactant 1

HCID 10863544HCID 10863544, compound

Product 1

HCID 86701273HCID 86701273, compoundYield 102.2%

Reagents, catalysts & solvents 2

HCID 23948RhodiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a 50 mL high pressure reactor with a magnetic stir bar was added (3S,6S,7R,8R)-8-benzyl-3-(tert-butoxycarbonylamino)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl isobutyrate (400 mg, 0.863 mmol) in THF (3 mL) to give a colorless solution. To the solution was added 5% Rh/C (50 mg, 0.024 mmol). After the reactor was sealed, it was purged with hydrogen gas (4 times). The reactor was charged to approximately 600 psi of H2 at room temperature (about 22° C.) and then the reaction was warmed to 70° C. and stirred at for 6 h. The reaction mixture was cooled, filtered, and concentrated. The residue was purified via column chromatography (SiO2, hexanes/EtOAc gradient) to afford the title compound (414 mg, 92%) as an off-white solid: 1H NMR (400 MHz, CDCl3) δ 5.32 (dd, J=39.3, 12.3 Hz, 2H), 5.01 (t, J=9.9 Hz, 1H), 4.94-4.72 (m, 2H), 3.58 (s, J=51.8 Hz, 1H), 2.72-2.51 (m, 2H), 1.78-1.52 (m, 6H), 1.45 (s, J=6.0 Hz, 9H), 1.26 (d, J=6.3 Hz, 3H), 1.20 (dd, J=7.0, 3.0 Hz, 6H), 1.19-1.04 (m, 4H), 1.02-0.68 (m, 3H); 13C NMR (101 MHz, CDCl3) δ 175.50, 172.74, 154.78, 133.68, 123.39, 80.39, 75.22, 74.50, 67.85, 65.49, 51.47, 47.36, 35.85, 35.40, 34.05, 34.01, 32.09, 28.19, 26.28, 26.00, 25.87, 18.95, 18.82, 17.77; ESIMS m/z 492 ([M+Na]+).

Workup

  1. customto give a colorless solution
  2. customAfter the reactor was sealed
  3. customit was purged with hydrogen gas (4 times)
  4. additionThe reactor was charged to approximately 600 psi of H2 at room temperature (about 22° C.)
  5. temperatureThe reaction mixture was cooled
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified via column chromatography (SiO2, hexanes/EtOAc gradient)

Sources & evidence

ORD record
ord-3548f0a6129a4fa0a517297e3cbbc763
Source dataset
uspto-grants-2015_09
Patent number
US09131690B2

Reaction notes

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