p-(Dimethoxymethyl)anisole → [(4R)-5,5-Dimethyl-2-(4-methoxyphenyl)-1,3-dioxan-4-yl]methan-1-ol

Participants

Reaction Steps

Following the general procedure for the transacetalization reaction of Description 6, 21.4 g (160.0 mmol) of (2R)-3,3-dimethylbutane-1,2,4-triol (6) was reacted in 400 mL of dichloromethane (DCM) in the presence of 932 μL (1.53 g, 10.0 mmol) of phosphorus(V) oxychloride (POCl3) with 45.6 g (250.0 mmol) of para-anisaldehyde dimethyl acetal. Two-fold purification by silica gel column chromatography using tert-butyl methyl ether (MTBE) and hexane (Hxn) mixtures as eluent (MTBE/Hxn=3:7→MTBE/Hxn=2:3→MTBE/Hxn=1:1→MTBE/Hxn=2:1→MTBE/Hxn=3:1) provided 26.7 g (66% yield) of the title compound (8a) as a pale-yellow liquid. Rf=0.26 (MTBE/Hxn=2:3). 1H NMR (400 MHz, CHCl3): δ=0.86 (s, 3H), 1.16 (s, 3H), 2.01-2.05 (m, 1H), 3.59-3.3.63 (m, 1H), 3.66-3.73 (m, 4H), 3.82 (s, 3H), 5.48 (s, 1H), 6.88-6.94 (m, 2H), 7.42-7.46 (m, 2H) ppm. MS (ESI) m/z: 253.1 (M+H)+. The analytical data for the compound was consistent with that given in the literature (Blakemore et al., J. Org. Chem. 2005, 70, 5449-5460; and Shiina et al., Bull. Chem. Soc. Jpn. 2001, 74, 113-122). Similar yields were obtained using camphorsulfonic acid (CSA) as the acidic catalyst.

Provenance & Evidence