Reaction Steps
To a stirred solution of epichlorohydrin (R)-2 (2 g, 21.6 mmol) in methanol (15 mL) was added 2-ethyl-6-methyl aniline (3.2 g, 23.7 mmol) and the resulting mixture was refluxed for 6 h at 70° C. After completion of the reaction (monitored by TLC), crushed KOH (3.0 g, 54.0 mmol) was added portion wise at temperature 10° C. After completing the addition, the reaction mixture was stirred vigorously for 8 h at 30° C. After completion of the reaction (monitored by TLC), excess methanol was evaporated under reduced pressure. The reaction mixture was then poured into water (20 mL) and extracted with EtOAc (2×15 mL). The combined organic layers were washed with brine (10 mL) and dried over Na2SO4. Evaporation of the solvent gave the crude residue which was purified by silica gel column chromatography using petroleum ether/EtOAc (90:10) as eluent to furnish (R)-1((2-ethyl-6-methylphenyl)amino)-3-methoxypropan-2-ol (R)-3 as a pale brown oil (4.6 g, 96%); [α]21D=+4.93 (c 2.09, CHCl3); IR (CHCl3, cm−1): νmax 3421, 3009, 2966, 1593, 1466, 1377, 1216, 1129, 968, 667; 1H NMR (400 MHz, CDCl3): δH 1.26 (t, J=7.5 Hz, 3H), 2.33 (s, 3H), 2.66-2.71 (m, 2H), 2.96-3.00 (dd, J=12.4, 7 Hz, 1H), 3.09-3.12 (dd, J=12.4, 3.9 Hz, 1H), 3.42 (s, 3H), 3.46-3.49 (dd, J=9.4, 6.3 Hz, 1H), 3.50-3.53 (dd J=9.7, 3.6 Hz, 1H), 3.96-4.00 (m, 1H), 6.91 (apparent t, J=7.2 Hz, 1H), 7.01 (d, J=7.3 Hz, 1H), 7.04 (d, J=7.6 Hz, 1H); 13C NMR (100 Hz, CDCl3): δC 145, 136.2, 130.6, 128.8, 126.7, 122.6, 75.3, 69.6, 59.2, 51.5, 24.2, 18.5, 14.8; MS: m/z 224 [M+1]+, 246 [M+Na]+.
