Fyles et al.
8
-(Tetrahydro-2H-pyran-2-yloxy)octanoic Acid (8). To a solu-
for 10 min and then filtered. This crystallization was repeated until
no more solids were produced. The filtrate was concentrated under
tion of cyclooctanone (65.42 g, 0.518 mol) and TFA (3 mL) in
dichloroethane (2 L) was added m-CPBA (192.8 g, 1.117 mol).
The mixture was heated at 70 °C for 2 days, and then the
temperature was lowered to 60 °C for an additional 3 days. The
mixture was allowed to cool to 50 °C at which point a saturated
reduced pressure to afford a colorless oil identified as 12 (3.18 g,
1
quantitative yield). H NMR (300 MHz, CDCl
3
): 0.05 and 0.06 (2
singlets, 6H), 0.82-0.88 (m, 12H), 1.24 (br, 18H), 1.50-1.63 (m,
2H), 2.51-2.66 (m, 4H), 3.95-4.10 (m, 2H), 4.52 (quintet, 1H, J
aqueous Na
2
SO
3
solution (500 mL) was added. A solution of
) 6 Hz); 13C NMR (75 MHz, CDCl
): -4.8, -4.7, 14.3, 18.1,
3
concentrated NaOH was added until the pH was about 12, which
resulted in a biphasic separation (deep orange, brown aqueous layer
and a yellow organic layer). The biphasic mixture was stirred
overnight. CH
concentrated HCl until the pH was 1-2. The aqueous layer was
removed, and then the organic layer was washed with NaHCO
22.9, 25.8, 26.1, 28.8, 29.5, 29.6, 29.71, 29.77, 29.84, 32.1, 42.4,
-
1
-1
42.6, 65.1, 66.3, 171.2, 177.0. IR: 1738 cm (s), 1713 cm (s).
HRLSIMS: Calcd for C23
431.320.
+
+
47 5
H O Si [M + H ]: 431.319 Found:
2 2
Cl (200 mL) was added and acidified with
Dimer 13 was prepared using the standard conditions in the
3
sequence given in Table 1, on Wang resin (0.259 g, 0.19 mmol) to
1
(
saturated) (3 × 1 L) and 1 M NaOH (3 × 1 L) to yield a yellow
produce 13 (8 mg; 0.022 mmol, yield 12%). H NMR (500 MHz,
organic layer. The organic layer was dried over MgSO
4
and
CDCl ): 1.20-1.65 (m, 28H), 2.27 (t, J ) 7.5 Hz, 2H), 2.33 (t, J
3
1
3
concentrated in Vacuo to yield a dark yellow oil (51.22 g) (partial
H NMR consistent with 5: 4.27, t, J ) 5.89 Hz; 2.38, t, J ) 6.62
Hz). The crude product was dissolved in dioxane (200 mL), and a
NaOH solution (300 mL, 2 M) was added with stirring and cooling
with an ice bath. The mixture was stirred and warmed to ambient
temperature over 5 h. The solution turned orange and was diluted
with CH
to pH 1-2 with concentrated HCl and then extracted with 100 mL
of CH Cl . The organic layer was washed with saturated NaCl (150
mL) and then dried over Na SO . The organic layer was concen-
trated in Vacuo to yield a yellow oil (partial H NMR consistent
with 6: 3.65, t, J ) 6.62 Hz; 2.35, t, J ) 7.72 Hz). The crude
product was dissolved in THF (160 mL), and with stirring under
an ice bath, a solution of DHP (32.9 mL, 360 mmol) and p-TsOH
) 7.5, 2H), 3.62 (t, J ) 6.6 Hz, 2H), 4.04 (t, J ) 6.6 Hz, 2H). C
NMR (125.75 MHz, CDCl ): 24.9, 25.1, 25.8, 26.1, 28.8, 29.1,
1
3
29.22, 29.24, 29.3, 29.37, 29.45, 29.54, 29.60, 29.63, 29.7, 32.85,
32.91, 33.9, 34.6, 63.2, 64.5, 64.7, 174.2, 177.9. HRLSIMS: Calcd
+
+
for NaC H O [M + Na ]: 381.2617 Found: 381.2523.
2
0
38
5
Trimer 14 was prepared using the standard conditions in the
Cl
2 2
(300 mL). The aqueous layer was isolated and acidified
sequence given in Table 1, on Wang resin (0.225 g, 0.17 mmol) to
1
produce 14 (19 mg; 0.038 mmol, yield 23%). H NMR (500 MHz,
2
2
CDCl ): 1.20-1.40 (m, 26H), 1.50-1.70 (m, 12H), 2.25-2.32 (m,
3
1
3
2
4
6H), 3.61 (t, J ) 6.6 Hz, 2H), 4.03 (t, J ) 6.6 Hz, 4H). C NMR
(125.75 MHz, CDCl ): 24.9, 25.1, 25.2, 25.7, 26.0, 26.1, 28.79,
1
3
28.84, 29.08, 29.15, 29.2, 29.28, 29.34, 29.42, 29.44, 29.6, 29.7,
32.8, 34.57, 34.59, 63.2, 64.5, 64.7, 174.20, 174.23, 174.3, 178.9.
+
+
HRLSIMS: Calcd for NaC H O
7
Found: 523.3606.
2
8
52
[M + Na ]: 523.3611
(
3.766 g, 19.8 mmol) in THF (40 mL) was added slowly. The
resulting solution was stirred for 3 h and then diluted with ether
600 mL) and washed with water (3 × 200 mL) and saturated NaCl
200 mL). The organic layer was then dried over Na SO . The crude
Dimer 15 was prepared using the standard conditions in the
(
(
sequence given in Table 1, on Wang resin (0.202 g, 0.15 mmol) to
1
2
4
produce 15 (10 mg; 0.022 mmol, yield 15%). H NMR (500 MHz,
product was purified on a silica gel column (380 g, 7 cm ID x 30
cm) with the eluent CHCl :MeOH (95:5) to yield a clear, colorless
oil identified as 8 (28.26 g, 22% yield from 4). H NMR (300 MHz,
CDCl ): 1.10-1.85 (m, 16H), 2.19 (t, 2H, J ) 7.4 Hz), 3.20-
.28 (m, 1H), 3.34-3.41 (m, 1H), 3.54-3.62 (m, 1H), 3.69-3.76
m, 1H), 4.47 (t, 1H, J ) 3.3 Hz), 10.9 (br s); 13C NMR (75 MHz,
CDCl ): 19.8, 24.8, 25.7, 26.2, 29.17, 29.24, 29.8, 30.9, 34.2, 62.5,
7.8, 99.0, 179.9. IR: 1736 cm (s), 1709 cm (s). HRLSIMS:
CDCl ): 0.86 (t, J ) 7 Hz, 3H), 1.19-1.70 (m, 30H), 2.20-2.35
3
3
(m, 2H), 2.50-2.60 (m, 4H), 4.08 (t, J ) 6.8 Hz, 4H), 4.41-4.46
1
13
(m, 1H). C NMR (125.75 MHz, CDCl ): 14.3, 22.9, 25.0, 25.8,
3
3
26.1, 28.6, 28.8, 29.0, 29.2, 29.5, 29.6, 29.7, 29.8, 29.85, 29.86,
32.1, 40.9, 40.9, 65.0, 65.1, 65.3, 172.3. HRLSIMS: Calcd for
3
(
+
+
NaC H O [M + Na ]: 481.3141 Found: 481.3139.
2
5
46
7
3
Trimer 16 was prepared using the standard conditions in the
-
1
-1
6
sequence given in Table 1, on Wang resin (0.202 g, 0.15 mmol) to
+
+
1
Calcd for C13
H
23
O
4
[M - H ]: 243.1596 Found: 243.1597.
produce 16 (44 mg; 0.067 mmol, yield 45%). H NMR (500 MHz,
1
2-(Tetrahydro-2H-pyran-2-yloxy)dodecanoic Acid (9). To a
CDCl ): 0.84 (t, J ) 7.0, 3H), 1.20-1.40 (m, 40H), 1.51-1.65
3
stirred suspension of 12-hydroxydodecanoic acid (9.180 g, 42.4
mmol) in THF (75 mL) under an ice bath was added a solution of
DHP (5.4 mL, 59 mmol) and p-TsOH (0.263 g, 1.24 mmol) in
THF (10 mL) dropwise. The resulting solution was stirred for an
additional 4.5 h at 5 °C. The solution was diluted with ether (120
mL) and washed with water (3 × 40 mL). The organic layer was
(m, 10H), 2.26 (t, J ) 7.5 Hz, 2H), 2.31 (t, J ) 7.5 Hz, 2H), 2.51-
1
3
2.53 (m, 4H), 4.01-4.08 (m, 6H), 4.40-4.45 (m, 1H). C NMR
(125.75 MHz, CDCl ): 14.3, 22.9, 24.9, 25.0, 25.86, 25.93, 26.05,
3
26.08, 28.6, 28.7, 28.76, 28.81, 29.0, 29.1, 29.15, 29.19, 29.22,
29.4, 29.5, 29.55, 29.59, 29.63, 29.68, 29.74, 29.80, 29.81, 32.1,
34.2, 34.5, 40.9, 64.6, 65.0, 65.1, 65.2, 172.07, 172.11, 174.1, 179.4.
+
dried over MgSO
4
and concentrated under reduced pressure to give
HRLSIMS: Calcd for NaC H O : 679.4761 Found: 679.4781.
3
7
68
9
a crude product. The crude product was purified on a silica gel
column (1.1 kg, 10 cm ID x 90 cm) using CHCl as eluent to afford
a clear colorless oil identified as 9 (12.104 g, 95% yield). H NMR
300 MHz, CDCl ): 1.20-1.90 (m, 25H), 2.31 (t, 2H, J ) 7.7
Hz), 3.31-3.39 (m, 1H), 3.45-3.51 (m, 1H), 3.66-3.74 (m, 1H),
.81-3.88 (m, 1H), 4.56 (t, 1H, J ) 3.3 Hz); 13C NMR (75 MHz,
CDCl ): 19.8, 24.9, 25.7, 26.4, 29.2, 29.4, 29.57, 29.65, 29.68,
9.71, 29.9, 30.9, 34.3, 62.5, 67.9, 98.99, 180.02. IR: 1736 cm
Tetramer 17 was prepared using the standard conditions in the
3
sequence given in Table 1, on Wang resin (0.227 g, 0.17 mmol) to
1
1
produce 17 (66 mg; 0.083 mmol, yield 49%). H NMR (500 MHz,
(
3
CDCl ): 0.85 (t, J ) 6.9 Hz, 3H), 1.20-1.65 (m, 60H), 2.26 (t, J
3
) 7.5 Hz, 4H), 2.32 (t, J ) 7.5 Hz, 2H), 2.52 (d, J ) 6.6 Hz, 4H),
3
4.03 (t, J ) 6.7 Hz, 4H), 4.07 (t, J ) 6.7 Hz, 4H), 4.43 (quintet,
J ) 6.3 Hz, 1H). 13C NMR (125.75 MHz, CDCl ): 14.3, 22.9,
3
3
-
1
2
24.8, 25.05, 25.08, 25.2, 25.88, 25.94, 26.07, 26.11, 28.65, 28.73,
28.77, 28.83, 29.0, 29.06, 29.11, 29.16, 29.20, 29.3, 29.43, 29.44,
29.5, 29.6, 29.7, 29.75, 29.81, 29.82, 32.1, 34.0, 34.5, 34.6, 40.9,
64.47, 64.51, 64.7, 65.0, 65.1, 65.2, 172.09, 172.11, 174.1, 174.2,
-
1
+
+
(
2
1
s), 1709 cm (s). HREIMS: Calcd for C17
H
32
31
O
4
[M - H ]:
: C, 67.96; H,
0.74; O, 21.30. Found: C, 67.82; H, 10.80; O, 21.33.
-(tert-Butyldimethylsiloxy)-5-oxo-5-(dodecyloxy)pentanoic Acid
12). To a stirred toluene solution (20 mL) of 3-(tert-butyldimeth-
ylsilyloxy)glutaric anhydride (1.9 g, 7.79 mmol) was added
-dodecanol (1.40 g, 7.49 mmol). The solution was stirred at reflux
99.222 Found: 299.222. Anal. Calcd for C17
H
O
4
+
+
3
179.0, 179.1. HRLSIMS: Calcd for NaC45
821.5755 Found: 821.5760.
82
H O11 [M + Na ]:
(
Dimer 18 was prepared using the standard conditions in the
1
sequence given in Table 1, on Wang resin (0.234 g, 0.18 mmol) to
1
overnight, and the solvent was removed under reduced pressure to
give a crude product. The crude product was dissolved in pentane
produce 18 (14 mg; 0.027 mmol, yield 15%). H NMR (500 MHz,
CDCl
3
): 0.86 (t, J ) 7.0 Hz, 3H), 1.20-1.65 (m, 41H), 2.25 (t, J
(80 mL) and cooled in a dry ice/ethanol bath for 10 min before
) 7.5 Hz, 2H), 2.67-2.78 (m, 4H), 3.64 (t, J ) 6.5 Hz, 2H), 4.05
(t, J ) 6.8 Hz, 2H), 5.48 (quintet, J ) 6.0 Hz, 1H). C NMR
1
3
filtration. The filtrate was cooled again in a dry ice/ethanol bath
8550 J. Org. Chem., Vol. 71, No. 22, 2006