1884
M. SARAVANAN ET AL.
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(4.1 g, 88.0%). Mass: 259.8 (Mþ1); IR (cmꢀ1): 3099 (Ar-H), 1611 (C C); H NMR
=
=
(CDCl3, d ppm): 7.1 (d, 2H, Ar-H), 6.8 (d, 2H, Ar-H), 5.6 (t, 1H, C CH), 3.8 (s,
3H, OCH3), 3.3 (t, 1H, Ph-CH-CH2), 2.6 (dd, 2H, CH2), 2.2 [s, 6H, N(CH3)2], 2.1
(t, 2H, cyclohexene), 1.8 (m, 2H, cyclohexene), 1.5 (m, 4H, cyclohexene); 13C
NMR (CDCl3, d ppm): 157.80, 139.27, 135.34, 128.70, 121.45, 113.53, 62.93,
55.16, 50.08, 45.98, 26.94, 25.35, 22.99, 22.52. CHN analysis calcd. for C17H25NO:
C, 78.72; H, 9.71; N, 5.40. Found. C, 78.65; H, 9.76; N, 5.47.
(2RS)-2-Cyclohexyl-2-(4-methoxyphenyl)-N,N-
dimethylethanamine (3)
To a mixture of 2 (5 g, 0.02 mol) and methanol (50 mL) in an autoclave
equipped with hydrogen gas inlet and gas induction stirring system, 5% wet Pd=C
(0.5 g) was charged. Temperature was maintained at 40–45 ꢂC for 3 h under
2–3 kg=cm2 hydrogen gas pressure and then cooled to 25–35 ꢂC. The catalyst was
filtered off, and the filtrate was concentrated under reduced pressure at less than
60 ꢂC to afford the title compound 3 (4.6 g, 92.0%). Mass: 262.3 (Mþ1); IR (cmꢀ1):
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3164 (Ar-H) 1245 & 1041 (C-O-C); H NMR (CDCl3, d ppm): 7.1 (d, 2H, Ar-H),
6.9 (d, 2H, Ar-H), 3.8 (s, 3H, OCH3), 3.6 (m, 1H, Ph-CH-CH2), 3.3 (dd, 1H,
CH2), 3.0 (dd, 1H, CH2), 2.2 (s, 6H, N(CH3)2), 0.9–1.7 (m, 11H, cyclohexyl);
13C NMR (CDCl3, d ppm): 158.89, 130.99, 129.37, 114.37, 61.22, 55.21, 46.61,
44.65, 43.53, 42.46, 39.13, 31.23, 29.71, 26.14, 26.08, 26.01. CHN analysis calcd.
for C17H27NO: C, 78.11; H, 10.41; N, 5.36. Found: C, 78.16; H, 10.50; N, 5.32.
1-[(1RS)-1-(4-Methoxyphenyl)-2-(methylamino)ethyl]-
cyclohexanol (5)
Formic acid (2.2 g, 0.048 mol) was added to a solution of 1-[(RS)-2-amino-
1-(4-methoxyphenyl)ethyl]cyclohexanol (free base of 4, 10 g, 0.04 mol) in toluene
(60 mL), and the mixture was heated to reflux for 5 h. The reaction mass was cooled
to 25–35 ꢂC and washed with saturated aqueous sodium bicarbonate solution
(150 mL). The toluene layer was washed with water (2 ꢃ 25 mL) and distilled off
completely under reduced pressure at less than 70 ꢂC to afford N-[2RS-(1-
hydroxycyclohexyl)-2-(4-methoxyphenyl)ethyl]formamide 5a (11 g, 99%). To a
solution of 5a (11 g, 0.04 mol) in THF (30 mL), 10 mol solution of boranedimethyl
sulfide (9.1 g, 0.12 mol) was slowly added and heated to reflux for 5 h. The reaction
mass was cooled to 0–5 ꢂC, quenched with methanol (50 mL), and concentrated under
reduced pressure at less than 60 ꢂC. The residual product was dissolved in DCM
(50 mL) and washed with water (30 mL). The DCM layer was distilled off completely
under reduced pressure to afford the title compound 5 (7.7 g, 73%). Mass: 264.3
1
(Mþ1); IR (cmꢀ1): 3500–3200 (OH), 3306 (N-H) 1243 & 1039 (C-O-C); H NMR
(CDCl3, d ppm): 7.1 (d, 2H, Ar-H), 6.9 (d, 2H, Ar-H), 3.9 (s, 3H, OCH3), 3.8
(m, 1H, Ph-CH-CH2), 3.3 (dd, 1H, CH2), 3.1 (dd, 1H, CH2), 2.7 (s, 3H, NCH3),
0.9–1.7 (m, 11H, cyclohexyl); 13C NMR (CDCl3, d ppm): 158.86, 130.49, 130.17,
113.88, 74.58, 55.24, 52.57, 50.83, 36.87, 33.91, 30.86, 25.36, 21.30, 21.16. CHN analy-
sis calcd. for C16H25NO2: C, 72.96; H, 9.57; N, 5.32. Found C, 72.91; H, 9.53; N, 5.36.