P. E. Duffy et al. / Tetrahedron 62 (2006) 4838–4843
4841
ꢁ
ꢀ78 and 0 C for 2 h before the solution was re-cooled to
1 equiv) and methanol (50 mL) was treated with concd
H2SO4 (0.5 mL) and heated to reflux for 12 h. On cooling
Et2O (80 mL) and 1 M KOH (80 mL) were added. The
resultant aqueous phase was further extracted with Et2O
(2ꢂ80 mL) and the combined organic phases were dried
over MgSO4. Filtration and solvent removal under reduced
pressure gave the crude methyl ester which was purified by
flash column chromatography (Hex–EtOAc, 19:1). Thus the
methyl ester (2.734 g, 61%) was isolated as a colourless
ꢁ
ꢀ78 C and heptanal (8.4 mL, 0.06 mol, 1.3 equiv) was
added dropwise. The mixture was stirred for 48 h during
which period room temperature was gradually reached.
EtOAc (250 mL) and 1 M HCl (250 mL) were added
and the resultant aqueous phase was further extracted
with EtOAc (2ꢂ250 mL). The combined organic phases
were dried over MgSO4 before filtration and solvent
evaporation under reduced pressure gave the crude cis-
alkene. Purification by flash column chromatography
(Hex–EtOAc, 6:1) afforded the product (9.03 g, 70%)
as a viscous yellow oil. Rf¼0.3 (Hex–EtOAc, 6:1);
ymax (neat/cmꢀ1) 3005, 2925, 2855, 1713, 1586, 1464;
dH (400 MHz, CDCl3) 0.89 (3H, t, J 7.0 Hz, CH3),
1.23–1.39 (20H, m, CH2), 1.64 (2H, pent, J 7.5 Hz,
CH2), 1.98–2.07 (4H, m, CH2), 2.36 (2H, t, J 7.5 Hz,
CH2), 5.34–5.41 (2H, m, CH), 11.20 (1H, br s, CO2H);
dC (100 MHz, CDCl3) 14.1, 22.6, 24.7, 27.15, 27.2,
29.0, 29.05, 29.2, 29.4, 29.5, 29.7, 31.8, 34.1, 129.8,
129.9, 179.9.
liquid. Rf¼0.25 (Hex–EtOAc, 19:1); ymax (neat/cmꢀ1
)
2926, 2854, 1737, 1436, 1246, 1196, 1169; dH (400 MHz,
CDCl3) 1.22–1.31 (10H, m, CH2), 1.42 (2H, pent, J
7.0 Hz, CH2), 1.63 (2H, pent, J 7.0 Hz, CH2), 1.84 (2H,
pent, J 7.5 Hz, CH2), 2.31 (2H, t, J 7.5 Hz, CH2), 3.39
(2H, t, J 7.0 Hz, CH2), 3.66 (3H, s, CH3); dC (100 MHz,
CDCl3) 24.9, 28.1, 28.6, 29.0, 29.1, 29.2, 29.3, 32.7,
33.95, 34.0, 51.4, 174.2.
3.1.5. 11-(1-Phenyl-1H-tetrazole-5-sulꢁfanyl)undecanoic
acid methyl ester. Under nitrogen at 0 C 60% w/w NaH
(0.48 g, 12.0 mmol, 1.1 equiv) was added in one portion
to a solution of 1-phenyl-1H-tetrazole-5-thiol 8 (1.96 g,
11.0 mmol, 1 equiv) in dry DMF (25 mL). After stirring
for 0.5 h the methyl ester (2.56 g, 11.0 mmol, 1 equiv) was
added. Stirring was maintained for 12 h. Et2O (50 mL) and
water (50 mL) were added and the resultant aqueous layer
was further extracted with Et2O (3ꢂ50 mL). The combined
ethereal extracts were dried over MgSO4. Filtration, solvent
removal in vacuo and purification by flash column chro-
matography (Hex–EtOAc, 4:1) gave the sulfide (3.29 g,
(b) Under nitrogen, a stirred slurry of (10-carboxydecyl)tri-
phenylphosphonium bromide 6 (10.0 g, 18.98 mmol,
ꢁ
1 equiv) in THF (120 mL) was cooled to ꢀ78 C. Potas-
sium bis(trimethylsilyl)amide (101 mL of 0.5 M solu-
tion in toluene, 50.49 mmol, 2.7 equiv) was added and
the mixture was warmed to room temperature over 2ꢁh.
The deep red solution was then re-cooled to ꢀ78 C
before heptanal (3.66 mL, 26.22 mmol, 1.4 equiv) was
added dropwise. The reaction was warmed to room tem-
perature and stirred for 12 h. Work-up and purification
was carried out as above and cis-vaccenic acid (4.76 g,
89%) was obtained whose data corresponded to the
above data.
ꢁ
80%) as a colourless waxy solid. Mp 34–36 C; Rf¼0.3
(Hex–EtOAc, 4:1); ymax (neat/cmꢀ1) 2925, 1736, 1598,
1500, 1386, 1242, 1170; dH (400 MHz, CDCl3) 1.25–1.38
(10H, m, CH2), 1.44 (2H, pent, J 7.5 Hz, CH2), 1.62 (2H,
pent, J 7.5 Hz, CH2), 1.83 (2H, pent, J 7.0 Hz, CH2), 2.34
(2H, t, J 7.5 Hz, CH2), 3.42 (2H, t, J 7.0 Hz, CH2), 3.69
(3H, s, CH3), 7.52–7.66 (5H, m, ArH); dC (100 MHz,
CDCl3) 24.9, 28.6, 29.0, 29.05, 29.1, 29.2, 29.3, 29.35,
33.3, 34.1, 51.5, 123.8, 129.8, 130.1, 133.7, 154.5, 174.3;
m/z (ES+) 399 (MNa+, 100%), 377 (MH+, 20%); found
377.1996, C19H29N4O2S requires 377.2011 (ꢀ4.0 ppm).
3.1.3. trans-Octadec-12-enoic acid (trans-vaccenic acid
4). With stirring cis-vaccenic acid (9.03 g, 32.02 mmol,
1 equiv) was treated with a solution of NaNO2 (0.47 g,
6.81 mmol, 0.2 equiv) in water (1.8 mL), which was heated
ꢁ
to 60 C. After 0.5 h a solution of concd HNO3 (2.3 mL) in
water (2.3 mL) was added. The mixture was further stirred
for 0.3 h before being removed from the oil bath. After
reaching room temperature (ca. 1 h) Et2O (30 mL) and water
(30 mL) were added. The resultant aqueous phase was fur-
ther extracted with Et2O (4ꢂ30 mL) and the combined
organic phases were dried over MgSO4 before filtration
and solvent evaporation under reduced pressure gave the
crude trans-alkene. Purification by three repetitive recrystal-
lisations from acetone afforded the product 4 (7.31 g, 81%)
3.1.6. 11-(1-Phenyl-1H-tetrazole-5-sulfonyl)undecanoic
ꢁ
acid methyl ester 7. At 0 C m-CPBA (1.38 g, 7.98 mmol,
3 equiv) was added in one portion to a solution of the sulfide
(1.00 g, 2.66 mmol, 1 equiv) in DCM (40 mL). Stirring was
maintained for two days. DCM (50 mL) and satd Na2SO3
(50 mL) were added and the mixture was partitioned for
1 h. The resultant aqueous layer was further extracted with
DCM (50 mL) and the combined organic extracts were
washed with satd NaHCO3 (100 mL). The resultant aqueous
layer was washed with DCM (3ꢂ50 mL) before drying over
MgSO4. Filtration and solvent removal in vacuo gave the sul-
ꢁ
as a white solid. Mp 43.5–44 C (acetone); Rf¼0.25 (Hex–
EtOAc, 6:1); ymax (Nujol/cmꢀ1) 2954, 2923, 2852, 1712,
1462, 1414, 1377; dH (400 MHz, CDCl3) 0.90 (3H, t, J
6.5 Hz, CH3), 1.24–1.39 (20H, m, CH2), 1.65 (2H, pent,
J 7.5 Hz, CH2), 1.95–2.04 (4H, m, CH2), 2.36 (2H, t, J
7.5 Hz, CH2), 5.38–5.47 (2H, m, CH2), 10.05 (1H, br s,
CO2H); dC (100 MHz, CDCl3) 14.1, 22.6, 24.6, 28.8, 29.0,
29.1, 29.2, 29.35, 29.4, 29.6, 31.7, 32.55, 32.6, 34.1,
1
fone 7 (1.02 g, 94%) as a colourless solid whose H NMR
spectruꢁm indicated sufficient purity for further use. Mp
47–49 C; Rf¼0.2 (Hex–EtOAc, 4:1); ymax (neat/cmꢀ1
)
+
2918, 2848, 1725, 1595, 1437, 1341, 1155; dH (400 MHz,
CDCl3) 1.22–1.40 (10H, m, CH2), 1.46–1.55 (2H, m,
CH2), 1.64 (2H, pent, J 7.5 Hz, CH2), 1.96 (2H, pent, J
8.0 Hz, CH2), 2.34 (2H, t, J 7.5 Hz, CH2), 3.68 (3H, s,
CH3), 3.74 (2H, t, J 8.0 Hz, CH2), 7.60–7.67 (3H, m,
ArH), 7.72 (2H, d, J 7.5 Hz, ArH); dC (100 MHz, CDCl3)
21.9, 24.9, 28.1, 28.8, 29.0, 29.05, 29.1, 29.2, 34.1, 51.5,
130.3, 130.4, 180.3; m/z (CI) 300 (MNH4 , 100%); found
300.28983, C18H38O2N requires 300.29025 (ꢀ1.5 ppm);
found C, 76.67; H, 11.85%; C18H34O2 requires C, 76.54;
H, 12.13%.
3.1.4. 11-Bromoundecanoic acid methyl ester.19 A solu-
tion of 11-bromoundecanoic acid (5.0 g, 19.00 mmol,