James and Snieckus
by recrystallization (hexane/Et2O) affording the title compound as
colorless plates (0.208 g, 82%). Mp 121-122 °C (hexane/Et2O).
IR (KBr) ν (max) 3402, 3085, 2978, 1629, 1593, 1515, 1470, 1387,
1329, 1282, 1177, 1068 cm-1; 1H NMR (250 MHz, CDCl3) δ 7.61
(s, 1H), 7.21 (d J ) 8.2 Hz, 1H), 7.09 (dd J ) 8.2, 7.4 Hz, 1H),
6.65 (dd J ) 7.4, 0.9 Hz, 1H), 6.37 (s, 1H), 4.65 (sept J ) 6.1 Hz,
1H), 1.38 (app t J ) 6.1 Hz, 12H); 13C NMR (62.9 MHz, CDCl3)
δ 150.7 (e), 149.2 (e), 148.3 (e), 131.0 (e), 124.2 (o), 120.2 (e),
118.7 (o), 111.8 (o), 107.4 (o), 106.2 (o), 71.9 (o), 21.9 (o); MS
(EI (70 eV)) m/e: (rel intensity) 260 (23), 218 (6.9), 176 (100),
147 (37); HRMS (EI (70 eV)) m/e calcd for C16H20O3: 260.1412,
found 260.1405.
(o), 56.0 (o), 55.8 (o), 42.1 (e), 41.9 (e), 22.0 (o), 22.0 (o), 14.2
(o), 13.3 (o); MS (EI (70 eV)) m/e: (rel intensity) 495 (M+, 26),
453 (1.0), 280 (11), 100 (100), 72 (38); HRMS (EI (70 eV)) m/e
calcd for C29H37NO6: 495.2622, found 495.2611.
N,N-Diethyl O-[6,7-Dihydroxy-2-(3,4-methoxyphenyl)]-1-
naphthylcarbamate (49c). To a solution of diisopropyl ether 49b
(0.197 g, 0.397 mmol) in CH2Cl2 (10 mL) at 0 °C was added BCl3
(2.40 mL, 1.0 mol/L in CH2Cl2). The reaction was allowed to stir
for 1 h and was then quenched with H2O (20 mL). The layers were
separated, and the aq phase was extracted with CH2Cl2 (2 × 20
mL). The combined organic layers were washed (H2O, brine), dried
(Na2SO4) and concentrated in Vacuo. The residue was purified by
recrystallization (hexane/CH2Cl2) affording N,N-Diethyl O-[6,7-
dihydroxy-2-(3,4-dimethoxy-phenyl)]-1-naphthyl-carbamate as col-
orless plates (0.145 g, 89%). mp 183-184 °C (hexane/CH2Cl2);
IR (KBr) ν (max) 3550-2550 (br), 3052, 2951, 1690, 1638, 1603,
N,N-Diethyl O-(6,7-Diisopropoxy)-1-naphthylcarbamate (46b).
According to general procedure A, a mixture of naphthol 45b (5.04
g, 19.38 mmol) K2CO3 (5.40 g, 39.07 mmol) and ClCONEt2 (3.70
mL, 29.07 mmol) in CH3CN (100 mL) was heated at reflux for
12 h. Standard workup followed by recrystallization (hexane/Et2O)
afforded the title compound as colorless needles (6.96 g, 84%).
Mp 113.5-114.5 °C (hexane/Et2O). IR (KBr) ν (max) 3056, 2980,
1
1579, 1514, 1420 cm-1; H NMR (250 MHz, CDCl3) δ 8.61 (s,
1H, exch), 8.53 (s, 1H, exch), 7.52 (d J ) 8.4 Hz, 1H), 7.24 (m,
3H), 7.09 (d J ) 1.3 Hz, 1H), 6.95-7.03 (m, 2H), 3.82 (s, 6H),
3.46 (q J ) 7.0 Hz, 2H), 3.29 (q J ) 7.0 Hz, 2H), 1.15 (t J ) 7.0
Hz, 3H), 1.05 (t J ) 7.0 Hz, 3H); 13C NMR (62.9 MHz, CDCl3) δ
154.6 (e), 149.9 (e), 149.6 (e), 147.8 (e), 147.3 (e), 143.7 (e), 132.5
(e), 130.8 (e), 129.8 (e), 126.3 (o), 125.1 (e), 124.3 (o), 122.4 (o),
114.1 (o), 112.7 (o), 110.5 (o), 105.1 (o), 56.2 (o), 42.5 (e), 14.6
(o), 13.6 (o); MS (EI (70 eV)) m/e: (rel intensity); 411 (M+, 85),
397 (2.0), 340 (1.6), 296 (1.9), 281 (3.6), 237 (1.5), 215 (2.1), 100
(100), 72 (34); Anal. Calcd for C23H25NO6: C, 67.14; H, 6.12; N,
3.41 found: C, 66.96; H, 6.21, N, 3.38.
1
2974, 1715, 1603, 1501, 1470, 1420 cm-1; H NMR (250 MHz,
CDCl3) δ 7.49 (d J ) 8.1 Hz, 1H), 7.29 (dd J ) 8.1, 7.6 Hz, 1H),
7.23 (s, 1H), 7.20 (s, 1H), 7.13 (dd J ) 7.6, 1.2 Hz, 1H), 4.59, (m,
2H), 3.41-3.59 (m, 4H), 1.40 (d J ) 6.1, Hz, 6H), 1.39 (d J )
6.1, Hz, 6H), 1.20-1.32 (m, 6H); 13C NMR (62.9 MHz, CDCl3) δ
154.1 (e), 149.4 (e), 149.3 (e), 146.3 (e), 130.9 (o), 123.6 (o), 123.5
(o), 123.3 (e), 116.2 (o), 112.3 (o), 105.5 (o), 71.8 (o), 71.7 (o),
42.3 (e), 42.0 (e), 21.9 (o), 14.4 (o), 13.4 (o); MS (EI (70 eV))
m/e: (rel intensity) 359 (M+, 29), 280 (0.26), 260 (0.40), 217 (1.0),
175 (7.0), 147 (11), 100 (100), 72 (45), 44 (11); Anal. Calcd for
C21H29NO4: C, 70.17; H, 8.13; N, 3.90; found: C, 70.26; H, 8.27;
N, 3.87.
N,N-Diethyl O-[6,7-Dimethoxymethoxy-2-(3,4-methoxyphe-
nyl)]-1-naphthylcarbamate (49d). To a suspension of NaH (1.20
g, 30.00 mmol) containing MOMCl (1.60 mL, 21.07 mmol) in dry
DMF (50 mL) at 0 °C was added a solution of N,N-Diethyl O-[6,7-
dihydroxy-2-(3,4-dimethoxy-phenyl)]-1-naphthyl-carbamate (49c)
in DMF (5 mL) dropwise. After the evolution of hydrogen had
ceased, the mixture was allowed to warm to rt over 2 h. The reaction
was then quenched by pouring slowly into 100 mL of H2O
containing ice. The resulting mixture was extracted with Et2O (3
× 50 mL), and the combined organic layers were washed with H2O
(5 × 100 mL), brine, dried (Na2SO4), and concentrated in Vacuo.
The residue was purified by column chromatography (1:1 hexane/
EtOAc) giving the title compound as a colorless glass (1.51 g, 95%).
N,N-Diethyl O-(2-Iodo-6,7-diisopropoxy)-1-naphthylcarbam-
ate (47b). According to general procedure B, carbamate 46b (0.692
g, 1.93 mmol) was treated sequentially with TMEDA (0.28 mL,
1.864 mmol), a solution of s-BuLi (1.40 mL, 1.41 mol/L) and I2
(0.552 g, 2.18 mmol). Standard workup followed by column
chromatography (6:1 hexane/EtOAc) afforded a the title compound
as a light-blue solid (0.654 g, 70%). Mp 102-103 °C (hexane/
Et2O). IR (KBr) ν (max) 2977, 2933, 1723, 1622, 1587, 1496, 1462,
1
1411 cm-1; H NMR (250 MHz, CDCl3) δ 7.58 (d J ) 8.6 Hz,
1H), 7.25 (d J ) 8.6 Hz, 1H), 7.13 (s, 1H), 7.11 (s, 1H), 4.49-4.61
(m, 2H), 3.57-3.66 (m, br, 2H), 3.43 (q J ) 7.1 Hz, 2H), 1.38 (t
J ) 6.3 Hz, 15H), 1.24 (t J ) 7.1 Hz, 3H); 13C NMR (62.9 MHz,
CDCl3) δ 152.4 (e), 149.8 (e), 149.6 (e), 146.8 (e), 132.5 (o), 130.4
(o), 125.3 (o), 124.4 (e), 111.8 (o), 105.5 (o), 86.6 (e), 71.7 (o),
71.6 (o), 42.3 (e), 42.1 (e), 21.8 (o), 21.7 (o), 14.5 (o), 13.3 (o);
MS (EI (70 eV)) m/e: (rel intensity) 485 (M+, 15), 358 (5.9), 301
(3.6), 273 (2.6), 174 (4.0), 100 (100), 72 (20); Anal. Calcd for
C21H28NO4I: C, 51.97; H, 5.81; N, 2.89; found: C, 52.00; H, 5.87;
N, 2.84.
IR (neat) ν (max) 2948, 2833, 1716, 1607, 1584, 1470, 1415 cm-1
;
1H NMR (250 MHz, CDCl3) δ 7.60 (d J ) 8.5 Hz, 1H), 7.56 (s,
1H), 7.51 (s, 1H), 7.36 (d J ) 8.5 Hz, 1H), 7.05-7.09 (m, 2H),
6.92 (d J ) 8.1 Hz, 1H), 5.38 (s, 2H), 5.35 (s, 2H), 3.91 (s, 3H),
3.89 (s, 3H), 3.55 (s, 3H), 3.53 (s, 3H), 3.49 (q J ) 6.6 Hz, 2H),
3.30 (q J ) 6.6 Hz, 2H), 1.21 (t J ) 6.6 Hz, 3H), 1.09 (t J ) 6.6
Hz, 3H); 13C NMR (62.9 MHz, CDCl3) δ 153.7 (e), 148.4 (e), 148.1
(e), 147.3 (e), 142.9 (e), 131.3 (e), 130.2 (e), 130.0 (e), 126.8 (o),
124.3 (e), 124.2 (o), 121.5 (o), 112.4 (o), 111.5 (o), 111.0 (o), 106.0
(o), 95.5 (e), 95.2 (e), 56.1 (o), 56.0 (o), 55.8 (o), 55.7 (o), 42.1
(e), 41.9 (e), 14.1 (o), 13.1 (o); MS (EI (70 eV)) m/e: (rel intensity)
499 (M+, 95), 467 (5.6), 455 (4.6), 437 (3.1), 399 (3.7), 350 (8.0),
336 (9.3), 323 (8.6), 292 (12), 265 (3.7), 165 (2.5), 100 (100), 72
(47); HRMS (EI (70 eV)) m/e calcd for C27H33NO8: 499.2206, found
499.2191.
N,N-Diethyl O-[6,7-Diisopropoxy-2-(3,4-dimethoxyphenyl)]-
1-naphthyl-carbamate (49b). According to general procedure F,
a solution of naphthylcarbamate 46b (1.81 g, 5.04 mmol) in THF
(20 mL) was sequentially treated with TMEDA (0.845 mL, 5.61
mmol), a solution of s-BuLi (4.70 mL, 1.18 mol/L), ZnCl2 (5.60
mL, 1.0 mol/L), a solution of 4-bromoveratrole (48a) (2.29 g, 10.55
mmol) in THF (10 mL) and Pd(PPh3)4 (130 mg, 0.112 mmol). The
reaction was heated at reflux for 12 h and standard workup followed
by column chromatography afforded the title compound as a
colorless oil (0.790 g, 32%). IR (neat) ν (max) 2978, 2935, 1712,
N,N-Diethyl 5,6-Dimethoxy-2-(1-hydroxy-6,7-bis(methoxyme-
thoxy)-2-naphthyl)benzamide (50c). Procedure 1. According to
general procedure C1, a solution of carbamate 49dc (0.463 g, 0.928
mmol) in THF (5 mL) was added to a solution of LDA (5.60 mmol)
in THF (10 mL) at 0 °C and the solution allowed to stir at rt for
6 h. Standard workup followed by column chromatography (3:2
hexane/EtOAc) afforded the title compound as a foam (0.114 g,
1606, 1500, 1469 cm-1 1H NMR (250 MHz, CDCl3) δ 7.55
;
(d J ) 8.4 Hz, 1H), 7.31 (d J ) 8.4 Hz, 1H), 7.22 (s, 1H), 7.18 (s,
1H), 7.04 (m, 2H), 6.92 (d J ) 8.0 Hz, 1H), 4.59 (2 overlapping
sept J ) 6.0 Hz, 2H), 3.91 (s, 3H), 3.88 (s, 3H), 3.40 (q J ) 7.0
Hz, 2H), 3.30 (q J ) 7.0 Hz, 2H), 1.40 (d J ) 6.0 Hz, 12H), 1.17
(t J ) 7.0 Hz, 3H), 1.08 (t J ) 7.0 Hz, 3H); 13C NMR (62.9 MHz,
CDCl3) δ 153.9 (e), 149.9 (e), 149.3 (e), 148.5 (e), 148.1 (e), 142.8
(e), 131.2 (e), 130.2 (e), 129.7 (e), 126.3 (o), 124.2 (e), 123.9 (o),
121.6 (o), 112.7 (o), 112.6 (o), 111.1 (o), 106.3 (o), 72.0 (o), 71.9
1
25%). H NMR (300 MHz, CDCl3) δ 8.71 (s, 1H, exch), 8.02 (s,
1H), 7.44 (s, 1H), 7.27 (d J ) 8.3 Hz, 1H), 7.05 (d J ) 8.3 Hz,
1H), 7.00 (d J ) 8.6 Hz, 1H), 6.95 (d J ) 8.6 Hz, 1H), 5.39 (s,
2H), 5.37 (s, 2H), 3.91 (s 6H), 3.56 (s, 3H), 3.55 (s, 3H), 3.40 (m,
1H), 3.21 (m, 1H), 3.04 (q J ) 7.2 Hz, 2H), 0.91-0.84 (m, 6H);
13C NMR (62.9 MHz, CDCl3) δ 169.6 (e), 151.6 (e), 148.9 (e),
4092 J. Org. Chem. Vol. 74, No. 11, 2009