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stirred for 12 h. Then, ice-cold 1N HCl (10 mL) and water (5 mL) were added and the product extracted
with ether:hexane (1:1), dried over Na2SO4, and concentrated affording the diastereomeric amides
(0.11 g, 68%). The diastereomeric mixture was separated by silica gel column chromatography using
benzene:ethyl acetate (9:1). The most mobile diastereoisomer corresponded to the (R)-2-methoxyamide
(Rf=0.8), while the (S)-2-methoxyamide (Rf=0.66) eluted next.
3.1.1. (R)-N-[(S)-1-(Naphthyl)ethyl]-2-methoxyhexadecanamide 1
[α]D25=−5.72 (c 0.035, CHCl3); FT-IR (neat) νmax: 3250 (NH), 3060, 2915, 2852, 1646 (C_O),
1546, 1472, 1378, 1126, 940, 781 cm−1; 1H NMR (CDCl3, 300 MHz): δ=0.88 (3H, t, J=6.5 Hz, CH3),
1.25–1.30 (26H, br s, CH2), 1.70 (3H, d, J=6.8 Hz, N-CHCH3), 3.37 (3H, s, -OCH3), 3.68 (1H, dd, J=4.7
and 6.3 Hz, H-2), 5.94 (1H, q, N-CHCH3), 6.76 (1H, br d, NH), 7.43–8.08 (7H, m, naphthyl); 13C NMR
(CDCl3, 75 MHz): δ=171.4 (s, C-1), 138.1 (s), 133.9 (s), 131.1 (s), 128.7 (d), 128.4 (d), 126.4 (d), 125.8
(d), 125.1 (d), 123.5 (d), 122.4 (d), 82.4 (d, C-2), 58.0 (q, -OCH3), 43.9 (d, N-CHCH3), 32.3 (t), 31.9
(t), 29.7 (t), 29.6 (t), 29.5 (t), 29.45 (t), 29.42 (t), 29.3 (t), 24.6 (t), 22.7 (t), 20.8 (q, N-CHCH3), 14.1 (q,
-CH3); GC–MS (70 eV) m/z (relative intensity): 439 [M]+ (6), 244 (3), 243 (14), 241 (3), 211 (4), 198
(4), 182 (6), 171 (5), 170 (19), 169 (14), 156 (19), 155 (100), 154 (23), 153 (19), 152 (6), 129 (7), 128
(9), 115 (6), 111 (7), 97 (20), 95 (5), 89 (5), 85 (7), 83 (26), 81 (9), 71 (37), 69 (30), 67 (10), 58 (10), 57
(36), 55 (41); HREIMS m/z: 439.3447 (calcd for C29H45NO2: 439.3450).
3.1.2. (S)-N-[(S)-1-(Naphthyl)ethyl]-2-methoxyhexadecanamide 2
[α]D25=−25.72 (c 0.035, CHCl3); FT-IR (neat) νmax: 3308 (NH), 2956, 2918, 2853, 1651 (C_O),
1527, 1470, 1454, 1110, 809, 779 cm−1; 1H NMR (CDCl3, 300 MHz): δ=0.88 (3H, t, J=6.7 Hz, CH3),
1.20–1.38 (26 H, br s, CH2), 1.67 (3H, d, J=6.7 Hz, N-CHCH3), 3.16 (3H, s, -OCH3), 3.63 (1H, dd,
J=4.3 and 6.7 Hz, H-2), 5.94 (1H, q, N-CHCH3), 6.76 (1H, br d, NH), 7.44–8.13 (7H, m, naphthyl); 13
C
NMR (CDCl3, 75 MHz): δ=171.6 (s, C-1), 138.1 (s), 133.9 (s), 131.1 (s), 128.8 (d), 128.4 (d), 126.5 (d),
125.9 (d), 125.2 (d), 123.5 (d), 122.6 (d), 82.4 (d, C-2), 58.2 (q, -OCH3), 43.9 (d, N-CHCH3), 32.6 (t),
31.9 (t), 29.7 (t), 29.6 (t), 29.5 (t), 29.45 (t), 29.36 (t), 24.7 (t), 22.7 (t), 20.7 (q, N-CHCH3), 14.1 (q,
CH3); GC–MS (70 eV) m/z (relative intensity): 439 [M]+ (3), 243 (12), 198 (4), 182 (6), 171 (4), 170
(15), 169 (12), 168 (11), 156 (19), 155 (100), 154 (23), 153 (18), 152 (6), 129 (8), 128 (10), 127 (11),
115 (7), 111 (8), 98 (3), 97 (22), 96 (3), 95 (7), 89 (6), 85 (9), 83 (32), 81 (10), 77 (5), 71 (51), 69 (40),
67 (14), 58 (15), 57 (54), 56 (10), 55 (61); HREIMS m/z: 439.3459 (calcd for C29H45NO2: 439.3450).
3.2. Methyl (R)-2-hydroxyhexadecanoate
To a solution of (ꢀ)-2-hydroxyhexadecanoic acid (0.086 g, 0.31 mmol) and butylated hydroxy
toluene (1 mg, BHT) in a mixture of vinyl acetate (1.0 mL) and THF (1.5 mL) (dried over molecular
sieves 4 Å and passed through an alumina column) was added the lipase Pseudomonas fluorescens
(0.101 g, Aldrich), and the mixture was stirred with heating at 65°C for 24 h. After cooling to rt,
the mixture was filtered and the filtrate was concentrated in vacuo. The resulting mixture of (R)-2-
hydroxyhexadecanoic acid and (S)-2-acetoxyhexadecanoic acid was methylated with an ethereal solution
of diazomethane to give the corresponding fatty acid methyl esters in quantitative yields. This product
was then chromatographed using silica gel as the stationary phase and benzene:hexane (1:1) as the mobile
phase, affording 0.027 g (>95% ee) of unreacted methyl (R)-2-hydroxyhexadecanoate and 0.049 g (47%
of the maximum expected of 50%) of methyl (S)-2-acetoxyhexadecanoate. The unreacted methyl (R)-2-
hydroxyhexadecanoate was then used for the next step.