2,4-DIMETHYL-6-PHENYL-DIHYDROPYRAN synthesis

Yield:30310-41-9 61%

Reaction Conditions:

with (1S)-10-camphorsulfonic acid in n-heptane;water at 98 - 100;

Steps:

1.a.i

i ) To 98 mL of heptane was added benzaldehyde (100 g, 0.94 mol), camphorsulfonic acid (0.26 g, 0.001 mol) dissolved in 0.3 g of water. The mixture was heated to a pot temperature of 98-100° C. Remove any water in the flask as a water/heptane azeotrope (78° C. boiling point). When the flask temperature has stabilized, begin the addition of methylisoprenol (73.6 g, 0.74 mol). Approximately 13.2 g of water will be removed azeotropically during the reaction. Let the reaction continue until water removal has stopped. This will be indicated by a 20° C. rise in the vapor temperature at the top of the column Slowly add 0.4 g sodium carbonate dissolved in 8 g of water to the flask. Check to make sure the pH is above 9. The two layers were separated and the aqueous phase extracted with 100 ml of ether. The two ethereal phases were combined, washed with 50 ml of water and 50 ml of brine and dried over Na₂SO₄. Filtration and concentration gave 161 g of oil. This oil was purified by vacuum distillation (68 to 100° C., 0.5 to 0.05 mbar) through a short path to give 100.5 g (61%) of a mixture of double bond isomers of 2-methyl-4-methylene-6-phenyltetrahydro-2H-pyran. (0038) ¹H NMR (400 MHz, CDCl₃): 7.40-7.36 (m, 2H), 7.35-7.30 (m, 2H), 7.27-7.22 (m, 1H), 4.78 (m, 2H), 4.32 (dd, J=2.3 Hz, 0.5 Hz, 1H), 3.58 (m, 1H), 2.42 (dt, J=2.7 Hz, 0.4 Hz, 1H), 2.24 (m, 2H), 2.03 (m, 1H), 1.30 (d, J=1.2 Hz, 3H). (0039) ¹³C NMR (100 MHz, CDCl₃): 22.0 (q), 42.3 (t), 42.7 (t), 74.9 (d), 80.4 (d), 108.6 (t), 125.9 (d), 127.5 (d), 128.4 (d), 142.6 (s), 144.8 (s).

References:

US2016/264910,2016,A1 Location in patent:Paragraph 0037; 0038; 0039