Reaktion #330839

Reaktionsgleichung

acetylene

4-Methoxybenzyl {(1R)-1-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]pent-4-yn-1-yl}carbamate

4-iodonitrobenzene

triethylamine

→

4-methoxybenzyl [(1R)-1-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]-5-(4-nitrophenyl)pent-4-yn-1-yl]carbamate

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe mixture degassed with nitrogen (bubble 15 min)
2. 2
   workup.ADDITIONThe mixture was poured into water (1200 m)
3. 3
   Extraktionextracted with EtOAc (3×300 mL)
4. 4
   WaschenThe combined organics were then washed with water (2×500 mL), sat. NaCl (200 mL)
5. 5
   Trocknendried over magnesium sulfate
6. 6
   Filtrationfiltered
7. 7
   Sonstigeevaporated under vacuum
8. 8
   SonstigeResidue was purified by MPLC (Horizon Biotage 2× Flash 65i)
9. 9
   Wascheneluting with a gradient of 0-30% ethyl acetate in hexane
10. 10
    Sonstigeto give 41 g (84%) as a dark red oil

Vorschrift

To a solution of acetylene (from Step E, 40 g, 80 mmol) and 4-iodonitrobenzene (21.8 g, 88 mmol) in anhydrous DMF (500 ml) was added triethylamine (111 mL, 797 mmol). Pd(dppf)Cl2 (1.95 g, 2.39 mmol) and copper(I) iodide (910 mg, 4.78 mmol) was added and the mixture degassed with nitrogen (bubble 15 min) and the resulting solution stirred at room temperature for 5 h. The mixture was poured into water (1200 m) and extracted with EtOAc (3×300 mL). The combined organics were then washed with water (2×500 mL), sat. NaCl (200 mL), dried over magnesium sulfate, filtered and evaporated under vacuum. Residue was purified by MPLC (Horizon Biotage 2× Flash 65i) eluting with a gradient of 0-30% ethyl acetate in hexane to give 41 g (84%) as a dark red oil. %). 1H NMR (500 MHz, CDCl3): 8.11-8.04 (m, 2H), 7.94-8.01 (m, 1H), 7.38-7.21 (m, 8H), 6.87 (d, J=8.4 Hz, 2H), 4.98 (s, 2H), 4.77-4.59 (m, 2H), 4.00-3.95 (m, 3H), 3.81 (s, 3H), 2.56 (t, J=7.1 Hz, H=2H), 2.00-1.95 (m, 1H), 1.66-1.61 (m, 1H), 0.93 (s, 9H), 0.10 (s, 3H), −0.10 (s, 3H). LC-MS: m/z (ES) 589.3 (MH)+, 611.2 (MNa)+.

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