Water → (3S,6S,7R,8S)-8-benzyl-3-(tert-butoxycarbonylamino)-6-methyl-4-oxo-1,5-dioxonan-7-yl isobutyrate

HRID 75743Notes

Reaction equation

HRID 75743 reaction equation
[C:1]([O:5][C:6](=[O:27])[NH:7][C@H:8]1[CH2:16][O:15][CH2:14][C@H:13]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@H:12]([OH:24])[C@H:11]([CH3:25])[O:10][C:9]1=[O:26])([CH3:4])([CH3:3])[CH3:2].[C:28](Cl)(=[O:32])[CH:29]([CH3:31])[CH3:30].O>N1C=CC=CC=1>[C:28]([O:24][C@@H:12]1[C@@H:13]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:14][O:15][CH2:16][C@H:8]([NH:7][C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:27])[C:9](=[O:26])[O:10][C@H:11]1[CH3:25])(=[O:32])[CH:29]([CH3:31])[CH3:30]

Participants

5

Reactant 3

HCID 962WaterHCID 62325Isobutyryl chlorideHCID 86701245tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-hydroxy-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamate

Product 1

HCID 86701234(3S,6S,7R,8S)-8-benzyl-3-(tert-butoxycarbonylamino)-6-methyl-4-oxo-1,5-dioxonan-7-yl isobutyrateYield 53%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl-(3S,7S,8R,9S)-7-benzyl-8-hydroxy-9-methyl-2-oxo-1,5-dioxonan-3-ylcarbamate (72 mg, 0.19 mmol) in pyridine (1 mL) at 0° C. was added isobutyryl chloride (80 μL, 0.76 mmol) and the solution was stirred at 0° C. for 2 h. The crude reaction mixture was warmed to room temperature, water (1 mL) was added, and the solution was stirred for 30 min. The reaction mixture was extracted with Et2O (3×) and the combined organic extracts were dried over Na2SO4, filtered, and concentrated. The crude product was purified by flash chromatography (silica gel, 20% EtOAc/hexanes, TLC Rf=0.5) to furnish (3S,6S,7R,8S)-8-benzyl-3-(tert-butoxycarbonylamino)-6-methyl-4-oxo-1,5-dioxonan-7-yl isobutyrate as a white foam (45 mg, 53%): 1H NMR (400 MHz, CDCl3) δ 7.31-7.11 (m, 5H), 5.14 (d, J=8.0 Hz, 1H), 5.03 (m, 1H), 4.94 (t, J=9.2 Hz, 1H), 4.66 (d, J=7.7 Hz, 1H), 3.89 (dd, J=11.7, 7.2 Hz, 1H), 3.56 (d, J=10.7 Hz, 1H), 3.46 (m, 1H), 3.35 (dd, J=11.4, 6.8 Hz, 1H), 2.71 (dd, J=13.9, 3.6 Hz, 1H), 2.58 (dt, J=13.9, 7.0 Hz, 1H), 2.25 (t, J=12.6 Hz, 1H), 2.04 (s, 1H), 1.43 (s, 9H), 1.32 (d, J=6.2 Hz, 3H), 1.21 (dd, J=7.0, 0.9 Hz, 6H); ESIMS m/z 471.9 ([M+Na]1).

Workup

  1. customThe crude reaction mixture
  2. temperaturewas warmed to room temperature
  3. stirringthe solution was stirred for 30 min
  4. extractionThe reaction mixture was extracted with Et2O (3×)
  5. dry with materialthe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography (silica gel, 20% EtOAc/hexanes, TLC Rf=0.5)

Sources & evidence

ORD record
ord-6062a5c982c0407a9a20e8354dcef0f4
Source dataset
uspto-grants-2014_09
Patent number
US08835462B2

Reaction notes

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