May 2009
Improved Preparation of 3-(1,1-Dimethylallyl)decursinol
561
Methyl 3-(4-(benzyloxy)-2-(3-methylbut-2-enyloxy) phenyl)
acrylate (8). 1.27 kg (4.45 mol) compound 7 was added to the
suspension of 1.24 kg (9.27 mol) K2CO3 and 120 g (0.73 mol)
KI in 15 L acetone, then the 620 mL (5.34 mol) 1-bromo-3-
methylbut-2-ene was added dropwise. The resulted mixture
was stirred at room temperature for 3 h, filtrated, and the filtra-
tion was concentrated. The obtained residue was dissolved in
8 L CH2Cl2, and the organic layer was washed by H2O and
saturated brine, dried over Na2SO4, filtrated, and concentrated
to oil. The oil was stirred in 3 L petroleum ether for 2 h, fil-
trated to obtain 1.2 kg 8 as white solid, yield 77%, mp 62–
Figure 1. Structures of 1 and its analogues.
1
63ꢀ, ref. [7] 59–61ꢀ; H NMR (300 MHz, deuteriochloroform):
d 1.76 (s, 3H), 1.82 (s, 3H), 3.79 (s, 3H), 4.55 (d, J ¼ 7.2 Hz,
2H), 5.06 (s, 2H), 5.48 (m, 1H), 6.42 (d, J ¼ 16 Hz, 1H), 6.55
(m, 2H), 7.37 (m, 6H), 7.63 (d, J ¼ 9 Hz, 1H).
Finnigan MAT-95/711 spectrometer. Melting points were
measured on a Buchi-510 melting point apparatus, which are
uncorrected. TLC analyses were performed on Merck silica gel
60 F254 plate.
7-(Benzyloxy)-6-(3-methylbut-2-enyl)-2H-chromen-2-one
(9). 400 g (1.1 mol) 8 was dissolved in 2 L N,N-diethyl-ben-
zenamine in 5 L reactor equipped with water segregator. The
solvent was heated to reflux under N2. During the removing of
methanol, the temperature of reaction mixture developed from
202ꢀ to 226ꢀ, reflux for another 3 h, cooled to room tempera-
ture. The mixture was added into 10 L of 2M hydrochloric
acid, extracted with ethyl acetate three times. The combined
organic layer was washed by saturated brine, dried over
Na2SO4, concentrated to obtain slurry, filtrated to obtain 713 g
9 as white solid, yield 65%, mp 102–103ꢀ, ref. [7] 104–
104.5ꢀ; 1H NMR (300 MHz, deuteriochloroform): d 1.66 (s,
3H), 1.76 (s, 3H), 3.37 (d, J ¼ 7.2 Hz, 2H), 5.06 (s, 2H), 5.30
(m, 1H), 6.25 (d, J ¼ 9 Hz, 1H), 6.83 (s, 1H), 7.21 (s, 1H),
7.42 (m, 5H,), 7.63 (d, J ¼ 9 Hz, 1H).
7-(Benzyloxy)-2H-chromen-2-one (6). 1.0 kg (6.18 mol)
compound 5 was added to the mixture of 2.0 kg (14.47 mol)
K2CO3, 0.1 kg KI (0.6 mol), and 12 L acetone and then, 0.86
kg (6.78 mol) benzyl chloride was added. The resulted mixture
was heated to reflux for 4 h, cooled to room temperature, fil-
trated, and the filtration was concentrated under decreased
pressure. The residue was dissolved in 20 L CH2Cl2, washed
with saturated NH4Cl solution and H2O, dried over Na2SO4,
concentrated, and filtrated to obtain 1.5 kg white solid 6, yield
96.4%, mp 151–154ꢀ, ref. [8] 153–155ꢀ. The spectroscopic
data correspond to those reported in the ref. [8].
Methyl 3-(4-(benzyloxy)-2-hydroxyphenyl)acrylate (7). 1.5
kg (6 mol) 6 was dissolved in the mixture of 16 L methanol
and 2.0 kg (37 mol) sodium methylate. The resulted mixture
was heated to reflux for 6 h, cooled to room temperature,
added to 40 L of 2.6M hydrochloric acid with stirring at 0ꢀ,
filtrated to obtain white solid. The solid was washed with
H2O, dried at 60ꢀ to obtain 1.27 kg 7 as white solid, yield
7-Hydroxy-6-(3-methylbut-2-enyl)-2H-chromen-2-one
(10). 355 g (1.1 mol) compound 9 was dissolved in the mix-
ture of 3.5 L ethanol, 500 mL H2O, and 10 g Raney Ni, the
resulted suspension was stirred under H2 at room temperature
for 24 h, filtrated, the filtration was concentrated to obtain
white solid 250 g 10, yield 98%, mp 133–135ꢀ, ref. [7] 133–
135ꢀ; 1H NMR (300 MHz, deuteriochloroform): d 1.75 (s,
3H), 1.79 (s, 3H), 3.38 (d, J ¼ 7.5 Hz, 2H), 5.34 (m, 1H),
1
75%, mp 182–183ꢀ, ref. [7] 184.5–186ꢀ; H NMR (400 MHz,
DMSO-d6): d 3.66 (s, 3H), 5.06 (s, 2H), 6.45 (d, J ¼ 16 Hz,
1H), 6.50 (s, 1H), 6.52 (d, J ¼ 7.2 Hz, 1H), 7.32–7.43 (m,
5H), 7.52 (d, J ¼ 7.2 Hz, 1H), 7.77 (d, J ¼ 16 Hz, 1H).
Scheme 1. Conditions: (a) benzyl chloride, K2CO3, KI, acetone, reflux, 96%; (b) sodium methoxide, methanol, 75%; (c) 1-bromo-3-methybut-2-
ene, K2CO3, KI, acetone, r.t., 77%; (d) N,N-diethylbenzenamine, reflux, 65%; (e) H2, Riney-Ni, ethanol, H2O; (f) 1-bromo-3-methylbut-2-ene,
K2CO3, KI, acetone, r.t., 70%; (g) N,N-diethylbenzenamine, reflux, 32%; (h) m-CPBA, CH2Cl2, 0ꢀC; (i) silica gel, 0ꢀC, 75%.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet