反应详情

温度

65 °C

To a 10 L flask under nitrogen was added the product from step (ii) above (700 g, 1.93 mol) and THF (5.59 L). This was followed by the addition of CuI (19.2 g, 0.1 mol), triethylamine (1.29 L, 9.27 mol) and ethynyltriisopropylsilane (389 g, 2.13 mol). The reaction was degassed and purged with nitrogen three times. Pd(PPh3)4 (125.5 g, 0.198 mol) was added and the reaction degassed and purged with nitrogen. The reaction was heated to 65° C. overnight, after which LC indicated 91% product and <1% starting material. The reaction mixture was concentrated in vacuo, then the residue was taken up in ethyl acetate (2 L) and put through a silica plug (2 kg), eluting with additional ethyl acetate (30 L). The product-containing fractions were concentrated in vacuo, then the crude product was dissolved in TBME (5 L) and extracted with 6 N HCl (5 L). The aqueous HCl phase was washed with TBME (2×5 L), before being basified with 6 N NaOH to pH 9-10. The product was then extracted with TBME (2×5 L), the organics were dried, filtered and concentrated in vacuo to give 635 g of the sub-title compound with a purity of >95% by 1H NMR (excluding solvents).

1. customThe reaction was degassed
2. custompurged with nitrogen three times
3. customthe reaction degassed
4. custompurged with nitrogen
5. concentrationThe reaction mixture was concentrated in vacuo
6. washeluting with additional ethyl acetate (30 L)
7. concentrationThe product-containing fractions were concentrated in vacuo
8. dissolutionthe crude product was dissolved in TBME (5 L)
9. extractionextracted with 6 N HCl (5 L)
10. washThe aqueous HCl phase was washed with TBME (2×5 L)
11. extractionThe product was then extracted with TBME (2×5 L)
12. customthe organics were dried
13. filtrationfiltered
14. concentrationconcentrated in vacuo