Butyn-2-one → tert-butyl ((3S,7S,8R,9S)-7-benzyl-9-methyl-2-oxo-8-(((E)-3-oxobut-1-en-1-yl)oxy)-1,5-dioxonan-3-yl)carbamate

HRID 75751Notes

Reaction equation

HRID 75751 reaction equation
[CH2:1]([C@@H:8]1[C@@H:16]([OH:17])[C@H:15]([CH3:18])[O:14][C:13](=[O:19])[C@@H:12]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:11][O:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:28][C:29](=[O:32])[C:30]#[CH:31]>C(Cl)Cl.C1N2CCN(CC2)C1>[CH2:1]([C@@H:8]1[C@@H:16]([O:17]/[CH:31]=[CH:30]/[C:29](=[O:32])[CH3:28])[C@H:15]([CH3:18])[O:14][C:13](=[O:19])[C@@H:12]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:11][O:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 15018Butyn-2-oneHCID 86701245tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-hydroxy-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamate

Product 1

HCID 86701244tert-butyl ((3S,7S,8R,9S)-7-benzyl-9-methyl-2-oxo-8-(((E)-3-oxobut-1-en-1-yl)oxy)-1,5-dioxonan-3-yl)carbamateYield 84.1%

Reagents, catalysts & solvents 2

HCID 9237DabcoCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-hydroxy-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamate (622 mg, 1.64 mmol, 1.00 equiv) in CH2Cl2 (16 mL, 0.10 M) at 0° C. (ice water bath) were added but-3-yn-2-one (0.192 mL, 2.46 mmol, 1.50 equiv) and DABCO (9 mg, 0.08 mmol, 0.05 equiv). The dark solution was removed from the cold bath, stirred at room temperature for 2 h, concentrated, and purified by automated silica gel column chromatography (5-50% EtOAc in hexanes) to provide tert-butyl ((3S,7S,8R,9S)-7-benzyl-9-methyl-2-oxo-8-(((E)-3-oxobut-1-en-1-yl)oxy)-1,5-dioxonan-3-yl)carbamate (617 mg, 84%) as an amorphous white solid: IR (ATR) 1753, 1707, 1631, 1600, 1497, 1367, 1158, 1077, 1021, 956, 909, 730, 700 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.47-7.35 (d, J=12.3 Hz, 1H), 7.35-7.25 (m, 1H), 7.25-7.16 (m, 1H), 7.16-7.04 (m, 2H), 5.84-5.71 (d, J=12.3 Hz, 1H), 5.16-5.07 (d, J=8.2 Hz, 1H), 5.07-4.95 (dq, J=9.3, 6.4 Hz, 1H), 4.72-4.57 (q, J=7.4 Hz, 1H), 4.01-3.85 (dd, J=11.6, 7.5 Hz, 1H), 3.82-3.67 (t, J=9.2 Hz, 1H), 2.14-2.05 (m, 1H), 3.59-3.49 (m, 1H), 3.49-3.40 (m, 1H), 3.36-3.23 (dd, J=11.1, 7.6 Hz, 1H), 2.97-2.86 (dd, J=13.8, 3.7 Hz, 1H), 2.45-2.30 (m, 1H), 2.21-2.14 (s, 3H), 2.14-2.05 (s, 1H), 1.49-1.41 (s, 9H), 1.41-1.36 (d, J=6.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 197.25, 172.15, 162.57, 138.45, 129.07, 128.58, 126.52, 108.48, 89.17, 80.33, 73.86, 72.57, 71.38, 52.71, 46.43, 35.29, 28.69, 28.26, 18.73, 14.20; HRMS-ESI (m/z) [M+Na]+ calc'd for C24H33NO7Na, 470.2149. found, 470.2160.

Workup

  1. customThe dark solution was removed from the cold bath
  2. concentrationconcentrated
  3. custompurified by automated silica gel column chromatography (5-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-cad7d778959b4c1aa0c9b9f3d3e7497a
Source dataset
uspto-grants-2014_09
Patent number
US08835462B2

Reaction notes

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