1108
J.-H. Kwak et al.
methylene chloride, was added 4-dimethylaminopyri- 3.80 (s, 3H).
dine (3.0 mg, 0.021 mmol), triethylamine (53 mg, 0.53
mmol), acetic anhydride (16 mg, 0.159 mmol). The Methyl 3-(4-ethoxyphenoxy)-4,5-dimethoxyben-
reaction mixture was stirred for 20 min at room tem- zoate (4h)
perature. The reaction mixture was neutralized by Yield 71%; 1H-NMR (CDCl3, 300 MHz):
δ
7.37 (s, 1H),
= 9.0 Hz), 6.85 (d, 2H,
= 7.0 Hz), 3.94 (s, 6H), 3.84 (s,
= 7.0 Hz).
sodium bicarbonate, extracted with EtOAc (3
extract was concentrated in vacuo. Purification by 9.0 Hz), 4.01 (q, 2H,
flash column chromatography (EtOAc-Hexanes = 1 : 3H), 1.41 (t, 3H,
×
). The 7.20 (s, 1H), 6.94 (d, 2H,
J
J =
J
J
1
5) gave acetylated obovatol
(CDCl3, 300 MHz): 7.14 (d, 2H,
2H, = 8.4 Hz), 6.76 (s, 1H), 6.65 (s, 1H), 6.03 - 5.82 zoate (4i)
(m, 2H), 5.06 (d, 4H, J = 15.2 Hz), 3.38 (d, 2H,
= 6.6 Yield 80%; IR (KBr) 1722, 1211, 1095 cm−1; 1H-NMR
Hz), 3.29 (d, 2H, = 6.6 Hz), 2.29 (s, 3H), 2.26 (s, 3H). (CDCl3, 300 MHz): 7.37 (s, 1H), 7.20 (s, 1H), 6.94 (d,
2H, = 9.0 Hz), 6.85 (d, 2H, = 9.0 Hz), 4.01 (q, 2H,
= 7.0 Hz), 3.94 (s, 6H), 3.84 (s, 3H), 1.41 (t, 3H,
(2.00 g, 10.86 mmol) 7.0 Hz).
2
(32 mg, 82%). H-NMR
δ
J
= 8.4 Hz), 6.95 (d, Methyl 3,4-dimethoxy-5-(4-propoxyphenoxy)ben-
J
J
J
δ
J
J
J
J =
Methyl 3-hydroxy-4,5-dimethoxybenzoate (3)
To a solution of methyl gallate
7
in DMF anhydrous was added potassium carbonate
(1.20 g, 8.69 mmol) under nitrogen atmosphere. The
Spectral data of 4b-4e, 4g and 5a-5h were reported
mixture was stirred for 30 min at room temperature. in our previous report (Lee et al., 2007).
To the mixture, was added methyl iodide (3.39 g,
23.89 mmol) drop by drop. The reaction mixture was
stirred for 2 h at room temperature and then extract-
3,4-Dimethox-5-(4-propoxyphenoxy)benzoic
acid (6)
ed with ether. The extract was concentrated in vacuo
.
The compound 1 (0.110 mmol) was dissolved in
The crude product was purified by flash column chro- KOH (aq.) (1 N, 2 mL)/ethanol (2 mL). The reaction
matography (EtOAc-Hexanes = 1 : 3) to afford methyl mixture was refluxed for 2 h. After cooling to room
ether
300 MHz):
(s, 3H), 3.89 (s, 3H), 3.88 (s, 3H).
3
(1.84 g, 80%) as a white solid. 1H-NMR (CDCl3, temperature, the mixture was acidified with 1 N HCl,
δ
7.28 (s, 1H), 7.18 (s, 1H), 6.02 (s, 1H), 3.94 extracted with Ethyl Acetate. The extract was dried
over anhydrous MgSO4, and concentrated in vacuo
.
The resulting acid was used in next reaction without
1
further purification. Yield 99%; H-NMR (Acetone-d6
7.43 (d, 1H, = 1.8 Hz), 7.18 (d, 1H,
copper acetate (0.1 eq) and triethyl amine (5.0 eq) in 1.8 Hz), 6.95 (d, 4H, = 3.6 Hz), 3.84-3.95 (m, 8H),
= 7.2 Hz), 1.02 (t, 3H, = 7.2 Hz).
,
General procedure for the preparation of (4a-4i)
To a mixture of
3
(1.0 eq), arylboronic acid (1.2 eq), 300 MHz):
δ
J
J =
J
methylene chloride was added activated 4 molecular 1.78 (s, 2H,
sieve. The reaction flask was sealed with septa stuck
J
J
by a 18 gauge needle. The reaction mixture was stirred
for 2.5 h at room temperature, and then filtered to
remove molecular sieve and copper salt. The filtrate
General procedure for the preparation of com-
pounds (7a-c)
To a solution of
2 (0.040 mmol) in dry methylene
was concentrated in vacuo and purified by flash chloride (3 mL) was added oxalyl chloride (0.400 mmol)
column chromatography (EtOAc-Hexanes = 1 : 3
: 5) to afford biaryl ether.
→
1
and DMF (catalytic amount). The reaction mixture
was stirred for 1 h at room temperature. After com-
pletion, the mixture was evaporated completely and
Methyl 3-(4-cyanophenoxy)-4,5-dimethoxyben- then dissolved in dry methylene chloride (1 mL). To
zoate (4a)
the solution, alcohol (0.040 mmol) was added and
7.60 (d, 2H, stirred for 30 min at room temperature. The reaction
Yield 60%; 1H-NMR (CDCl3, 300 MHz):
δ
J
= 8.8 Hz), 7.52 (s, 1H), 741 (s, 1H), 6.97 (d, 2H,
J
=
mixture was extracted with Ethyl Acetate, washed
with brine, dried over anhydrous MgSO4, filtered and
concentrated. The residue was purified by flash column
8.8 Hz), 3.96 (s, 3H), 3.90 (s, 3H), 3.83 (s, 3H).
Methyl 3,4-dimethoxy-5-(4-vinylphenoxy)benzo- chromatography to afford ester 7.
ate (4f)
Yield 89%; lH-NMR (CDCl3, 300 MHz):
δ
7.47 (s, 1H), Butyl 3,4-dimethoxy-5-(4-propoxyphenoxy)ben-
= 8.7 Hz), 7.25 (s, 1H), 6.88 (d, 2H, zoate (7a)
8.7 Hz), 6.74-6.64 (m, 2H), 5.68 (d, 1H,
= 17.7 Hz), Yield 90%; 1H-NMR (Acetone-d6, 300 MHz):
5.16 (d, 1H, = 10.8 Hz), 3.92 (s, 3H), 3.84 (s, 3H), 1H, = 1.8 Hz), 7.17 (d, 1H, = 1.8 Hz), 6.95 (s, 4H),
7.40 (d, 2H,
J
J =
J
δ 7.41 (d,
J
J
J