Reaktion #164139

Reaktionsgleichung

5′-O-tert-butyldimethylsilyloxy-(5-(4-(N-trifluoroacetyl-2-aminoethoxy)but-2-yn-1-yl))-2′,3′-dideoxyuridine

undec-7-ene

1,5′-O-tert-butyldimethylsilyloxy-5-bromomethyl-2′,3′ dideoxyuridine

5′-O-tert-butyldimethylsilyloxy-5-bromomethyl-2′,3′-dideoxyuridine

copper

acetylide

3-(N-trifluoroacetyl-2-aminoethoxy)prop-1-yne

copper iodide

→

CuI

3-(N-trifluoroacetyl-2-aminoethoxy)prop-1-yne

DBU

Reaktionsbedingungen

Vorschrift

Next, 5′-O-tert-butyldimethylsilyloxy-5-bromomethyl-2′,3′-dideoxyuridine (3) can be coupled with an alkyne, in this case 3-(N-trifluoroacetyl-2-aminoethoxy)prop-1-yne, to form the 5′-O-tert-butyldimethylsilyloxy-(5-(4-(N-trifluoroacetyl-2-aminoethoxy)but-2-yn-1-yl))-2′,3′-dideoxyuridine (4). It will be readily appreciated by one of skill in the art that the coupling of an alkyl halide with an alkyne can be carried out by a number of methods known in the art. Without being limiting in any way, one example of such a method known in the art is the so-called Castro-Stephens coupling, see for example, White, J. D., et. al. J. Am. Chem. Soc., 123(23), 5407-5413 (2001) and Stephens, R. D., et. al. J. Org. Chem., 28, 3313 (1963). For example, as shown in Scheme 1,5′-O-tert-butyldimethylsilyloxy-5-bromomethyl-2′,3′ dideoxyuridine (3) can be contacted with a mixture comprising a copper reagent, for example copper iodide (CuI), an alkyne, for example 3-(N-trifluoroacetyl-2-aminoethoxy)prop-1-yne, and a base, for example 1,8-diazobicyloclo[5.4.0]undec-7-ene (DBU), to form 5′-O-tert-butyldimethylsilyloxy-(5-(4-(N-trifluoroacetyl-2-aminoethoxy)but-2-yn-1-yl))-2′,3′-dideoxyuridine (4), where an acetylide anion is formed in the mixture comprising CuI, 3-(N-trifluoroacetyl-2-aminoethoxy)prop-1-yne, and DBU.

Quelle