1,3-Propanediol → 3-[3-(5-Chloro-2-methoxyphenylsulfonyloxy)-5-methylphenoxy]propanol

Participants

Reaction Steps

Tri-n-butylphosphine (7.6 mL, 30.4 mmol) was added dropwise over 20 min to 3-(5-chloro-2-methoxyphenylsulfonyloxy)-5-methylphenol (5.00 g, 15.2 mmol, as prepared in step a of example 8), 1,3-propanediol (3.3 mL, 45.6 mmol) and 1,1'-(azodicarbonyl)dipiperidine (7.68 g, 30.4 mmol) in anhydrous tetrahydrofuran (80 mL) at 0° C. under a nitrogen atmosphere. Dichloromethane (150 mL) was added mid-way through the tri-n-butylphosphine addition to aid stirring. The slurry was stirred for an additional 5 min at 0° C. then at ambient temperature for 3 h. Diethyl ether (400 mL) was added, and the mixture was stirred for 10 min then filtered. The filtrate was concentrated and the product was purified by flash column chromatography (25% to 60% ethyl acetate in hexane) to give the title compound (4.07 g, 69%) as a gold oil. 1H-NMR (300 MHz, CDCl3) δ 7.82 (d, 1 H, J=2.8 Hz), 7.56 (dd, 1 H, J=2.6, 8.9 Hz), 7.03 (d, 1 H, J=8.9 Hz), 6.62 (br s, 1 H), 6.52 (br s, 1 H), 6.47 (t, 1 H, J=2.3 Hz), 4.03 (t, 2 H, J=6 Hz), 4.01 (s, 3 H), 3.80-3.85 (m, 2 H), 2.26 (s, 3 H), 2.00 (pentet, 2H, J=6 Hz), 1.64 (t, 1 H, J=5 Hz). Mass spectrun (MALDI-TOF, α-cyano-4-hydroxycinnamic acid matrix) calcd. for C17H19ClO6S: 409.0 (M+Na). Found: 409.0.

Provenance & Evidence