4060
G. Zhao et al. / Bioorg. Med. Chem. 13 (2005) 4056–4062
6.69 (d, J = 8.6 Hz, 1H), 4.88 (q, J = 6.7 Hz, 1H), 2.84
(q, J = 7.2 Hz, 2H), 2.25 (s, 3H), 2.14 (s, 3H), 1.53 (d,
J = 6.8 Hz, 3H), 1.03 (t, J = 7.2 Hz, 3H).
IV-15: [2-fluoro-4-(1-oxobutyl)phenoxy]acetic acid, yel-
low powder, yield 39.3%, mp 102–105 ꢁC, TLC
Rf = 0.58 (petroleum ether/acetone, 2:1, v/v). H NMR
1
(DMSO-d6) d: 13.40 (s, 1H), 7.82 (m, 2H), 7.23 (m,
1H), 4.92 (s, 2H), 2.99 (t, J = 7.1 Hz, 2H), 1.67 (m,
2H), 0.97 (t, J = 7.3 Hz, 3H).
IV-7: [3-bromo-4-(1-oxopropyl)phenoxy]acetic acid,
yellow powder, yield 69.0%, mp 96–98 ꢁC, TLC Rf =
0.51 (petroleum ether/acetone, 1:1, v/v). 1H NMR
(DMSO-d6) d: 13.12 (s, 1H), 7.69 (d, J = 8.6 Hz, 1H),
7.29 (d, J = 2.4 Hz, 1H), 7.08 (dd, J = 2.4, 8.6 Hz, 1H),
4.85 (s, 2H), 2.95 (q, J = 7.3 Hz, 2H), 1.12 (t,
J = 7.2 Hz, 3H).
3.3. General methods for preparing target compounds VI
Compounds IV (17 mmol) and 30% formaldehyde solution
(1.7 mL, 17 mmol) were added to ethanol (34 mL) fol-
lowing by addition of potassium carbonate (2.3 g,
17 mmol) in a mixed solution of water (17 mL) with eth-
anol (10 mL). The solution was added in ethanol
(24 mL) while stirring simultaneously. The mixture
was refluxed for 3 h and decanted into hydrochloric acid
solution (a mixture of 5 mL concentrated hydrochloric
acid and 340 mL water) after cooling down to room
temperature. The yielded yellow oil was extracted twice
with ether (150 mL) and the ether fraction was evapo-
rated to obtain a yellow product, which was then puri-
fied through a silica gel column using petroleum ether/
chloroform/methanol (10:10:1, v/v) as eluent.
IV-8: [2-chloro-4-(1-oxobutyl)phenoxy]acetic acid, white
powder, yield 87.7%, mp 115–118 ꢁC, TLC Rf = 0.67
(petroleum ether/acetone, 1:1, v/v). H NMR (DMSO-
1
d6) d: 13.10 (s, 1H), 7.97 (d, J = 2.1 Hz, 1H), 7.90 (dd,
J = 2.1, 8.7 Hz, 1H), 7.13 (d, J = 8.7 Hz, 1H), 4.90 (s,
2H), 2.94 (t, J = 7.1 Hz, 2H), 1.61 (m, 2H), 0.91 (t,
J = 7.4 Hz, 3H).
IV-9: [2-chloro-4-(1-oxopropyl)phenoxy]acetic acid, yel-
low powder, yield 59.8%, mp 117–119 ꢁC, TLC Rf =
1
0.59 (hexane/EtOAc, 2:3, v/v). H NMR (DMSO-d6) d:
13.10 (s, 1H), 7.98 (s, 1H), 7.89 (d, J = 8.7 Hz, 1H),
7.14 (d, J = 8.7 Hz, 1H), 4.92 (s, 2H), 2.99 (q, J = 7.1
Hz, 2H), 1.06 (t, J = 7.1 Hz, 3H).
VI-1: 2-[2-methyl-4-(2-methylene-1-oxopropyl)phenoxy]-
propionic acid, brown oil, yield 28.6%, TLC Rf = 0.54
1
(petroleum ether/acetone, 2:1, v/v). H NMR (DMSO-
IV-10: 2-[2-chloro-4-(1-oxopropyl)phenoxy]propionic acid,
yellow powder, yield 70.3%, mp 75–78 ꢁC, TLC Rf =
0.44 (petroleum ether/acetone, 2:1, v/v). 1H NMR
(DMSO-d6) d: 13.19 (s, 1H), 7.97 (d, J = 2.1 Hz, 1H),
7.90 (dd, J = 2.1, 8.7 Hz, 1H), 7.07 (d, J = 8.7 Hz, 1H),
5.09 (q, J = 6.7 Hz, 1H), 2.98 (q, J = 7.2 Hz, 2H), 1.57
(d, J = 6.8 Hz, 3H), 1.06 (t, J = 7.2 Hz, 3H).
d6) d: 13.06 (s, 1H), 7.80 (d, J = 8.6 Hz, 1H), 7.78 (s,
1H), 6.86 (d, J = 8.5 Hz, 1H), 5.87 (s, 1H), 5.47 (s,
1H), 4.96 (q, J = 6.6 Hz, 1H), 2.23 (s, 3H), 1.56 (d,
J = 6.7 Hz, 3H), 1.06 (s, 3H); MS: m/z = 249.5
(M++1); IR (KBr) mmax: 3435, 3060, 2979, 2938, 2911,
1731, 1711, 1669, 1599, 1498 cmꢀ1
.
VI-2: [2-methyl-4(2-methylene-1-oxopropyl)phenoxy]-
acetic acid, white powder, yield 39.0%, mp 112–
114 ꢁC, TLC Rf = 0.17 (petroleum ether/acetone, 2:1,
IV-11: 2-[2-chloro-4-(1-oxobutyl)phenoxy]propionic acid,
yellow oil, yield 80.5%, TLC Rf = 0.66 (petroleum ether/
acetone, 2:1, v/v). 1H NMR (DMSO-d6) d: 13.23 (s, 1H),
8.04 (s, 1H), 7.95 (d, J = 8.7 Hz, 1H), 7.12 (d,
J = 8.7 Hz, 1H), 5.16 (q, J = 6.8 Hz, 1H), 3.00 (t,
J = 7.2 Hz, 2H), 1.66 (m, 2H), 1.63 (d, J = 6.8 Hz,
3H), 0.96 (t, J = 7.4 Hz, 3H).
1
v/v). H NMR (DMSO-d6) d: 13.07 (s, 1H), 7.82 (d,
J = 8.6 Hz, 1H), 7.80 (s, 1H), 6.94 (d, J = 8.5 Hz, 1H),
4.85 (s, 2H), 3.69 (s, 2H), 2.29 (s, 3H), 1.06 (s, 3H); MS:
m/z = 234.8 (M+); IR (KBr) mmax
:
3398, 3059,
2972, 2939, 1743, 1658, 1599, 1502 cmꢀ1
.
IV-12: [2-fluoro-4-(1-oxopropyl)phenoxy]acetic acid,
yellow powder, yield 88.8%, mp 104–106 ꢁC, TLC
Rf = 0.45 (petroleum ether/acetone, 2:1, v/v). H NMR
(DMSO-d6) d: 13.20 (s, 1H), 7.76 (m, 2H), 7.19 (m,
1H), 4.89 (s, 2H), 2.98 (q, J = 7.2 Hz, 2H), 1.06 (t,
J = 7.2 Hz, 3H).
VI-3: 2-[2-methyl-4-(2-methylene-1-oxobutyl)phenoxy]-
propionic acid, yellow oil, yield 21.8%, TLC Rf = 0.26
(petroleum ether/chloroform/methanol, 5:5:1). 1H
NMR (DMSO-d6) d: 7.72 (d, J = 8.3 Hz, 1H), 7.68 (d,
J = 8.6 Hz, 1H), 6.98 (s, 1H), 4.46 (s, 2H), 3.64 (q,
J = 6.8 Hz, 1H), 3.54 (q, J = 7.2 Hz, 2H), 1.77 (s, 3H),
1.45 (d, J = 6.6 Hz, 3H), 0.78 (t, J = 7.4 Hz, 3H); MS:
m/z = 263.3 (M++1); IR (KBr) mmax: 3373, 2966, 2937,
1
IV-13: 2-[2-fluoro-4-(1-oxobutyl)phenoxy]propionic acid,
yellow oil, yield 72.5%, TLC Rf = 0.47 (petroleum ether/
acetone, 2:1, v/v). 1H NMR (DMSO-d6) d: 13.04 (s, 1H),
7.78 (m, 2H), 6.85 (m, 1H), 4.95 (q, J = 6.7 Hz, 1H), 2.90
(t, J = 7.2 Hz, 2H), 1.60 (m, 2H), 1.55 (d, J = 6.8 Hz,
3H), 0.91 (t, J = 7.4 Hz, 3H).
2877, 1669, 1614, 1513 cmꢀ1
.
VI-4: 2-[2,3-dimethyl-4-(2-methylene-1-oxobutyl)pheno-
xy]propionic acid, yellow powder, yield 83.7%, mp 115–
118 ꢁC, TLC Rf = 0.57 (petroleum ether/acetone, 2:1, v/
v). 1H NMR (DMSO-d6) d: 12.86 (s, 1H), 7.04 (d,
J = 8.5 Hz, 1H), 6.73 (d, J = 8.4 Hz, 1H), 5.91 (s, 1H),
5.47 (s, 1H), 4.86 (q, J = 6.8 Hz, 1H), 2.39 (q, J =
7.4 Hz, 2H), 2.16 (s, 3H), 2.12 (s, 3H), 1.55 (d,
J = 6.7 Hz, 3H), 1.07 (t, J = 7.4 Hz, 3H); MS: m/z =
277.4 (M++1); IR (KBr) mmax: 2962, 2938, 2878, 1726,
IV-14: 2-[2-fluoro-4-(1-oxopropyl)phenoxy]propionic acid,
yellow oil, yield 88.2%, TLC Rf = 0.47 (petroleum ether/
acetone, 2:1, v/v). 1H NMR (DMSO-d6) d: 13.26 (s, 1H),
7.82 (m, 2H), 7.16 (m, 1H), 5.15 (q, J = 6.8 Hz, 1H), 3.42
(q, J = 7.2 Hz, 2H), 1.61 (d, J = 6.8 Hz, 3H), 1.12 (t,
J = 7.2 Hz, 3H).
1708, 1650, 1591, 1578, 1482 cmꢀ1
.