2,6-Dimethyl-4-phenyl-phenol → 3-(t-Butyldimethylsilyloxymethyl)-5-[3-[2,6-dimethyl-4-phenylphenoxy]-propyl]-isoxazole

Participants

Reaction Steps

3-(Hydroxymethyl)-5-[3-[2,6-dimethyl-4-phenylphenoxy]-propyl]-isoxazole was prepared following procedures described in the literature; J. Med. Chem. (1994) 37 2421, thus 3-(t-butyldimethylsilyloxymethyl)-5-(3-hydroxypropyl)isoxazole (ibid.) and 2,6-dimethyl-4-phenyl-phenol were coupled by way of a Mitsunobu reaction to give the adduct, 3-(t-butyldimethylsilyloxymethyl)-5-[3-[2,6-dimethyl-4-phenylphenoxy]-propyl]-isoxazole in 82% yield. 1H nmr (CDCl3): δ=7.6-7.2 (m, 7H); 6.13 (s, 1); 4.75 (d, 2H); 3.86 (t, 2H); 3.07 (t, 2H); 2.33 (s, 6H); 2.23 (m, 2H) and 2.1 (t, OH). MS (ES): (M+H) 338.1748 (calc. C21H24NO3 338.1750). Removal of the silyloxy group under acidic hydrolysis gave the hydroxy compound, 3-(hydroxymethyl)-5-[3-[2,6-dimethyl-4-phenylphenoxy]-propyl]-isoxazole in 93% yield. 1H mm (CDCl3): δ=7.6-7.2 (m, 7H); 6.13 (s, 1H); 4.75 (d, 2H); 3.86 (t, 2H); 3.07 (t, 2H); 2.33 (s, 6H); 2.23 (m, 2H) and 2.1 (t, OH). MS (ES): (M+H) 338.1748 (calc. C21H24NO3 338.1750). Bromination of the hydroxy compound following the procedure of example 1 gave the bromomethyl compound, 3-(bromomethyl)-5-[3-[2,6-dimethyl-4-phenylphenoxy]-propyl]-isoxazole in 95% yield. 1H nmr (CDCl3): δ=7.6-7.2 (m, 7H); 6.17 (s, 1H); 4.41 (s, 2H); 3.86 (t, 2H); 3.07 (t, 2H); 2.33 (s, 6H) and 2.23 (m, 2H). MS(ES): (M+Na)+ 422.0725 (calc. C21H22BrNO2Na 422.0720).

Provenance & Evidence