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Organic & Biomolecular Chemistry
Page 5 of 10
DOI: 10.1039/C8OB01512K
Journal Name
ARTICLE
1200, 1254 cm-1 1H NMR (400 MHz, CDCl3) δ 7.71 – 7.66 (m, 1H),
7.53 (d, J = 7.8 Hz, 1H), 7.41 (t, J = 7.3 Hz, 1H), 7.27 – 7.21 (m, 1H),
6.75 (d, J = 15.7 Hz, 1H), 6.16 (dt, J = 15.6, 7.0 Hz, 1H), 6.13 (s, 1H),
3.61 (t, J = 6.6 Hz, 2H), 3.51 (q, J = 6.3 Hz, 2H), 3.17 (t, J = 6.5 Hz,
2H), 2.18 (dt, J = 7.7, 4.0 Hz, 2H), 1.95 (s, 3H), 1.57 – 1.27 (m, 10H)
13C NMR (100 MHz, CDCl3) δ 194.78, 170.43, 136.64, 135.75, 134.84,
131.96, 128.41, 127.13, 126.98, 126.63, 62.97, 39.73, 33.12, 32.77,
29.34 (2C), 29.30, 29.05, 28.99, 25.69, 23.22. HRMS (ESI+): calcd for
C21H31NO3S 400.1922 (M+Na), obsd. 400.1920.
(Spark Holland) solid-phase extraction module using HySphere
Resin GP cartridges. Compounds were eluted off the cartridges
with d3-acetonitrile and analyzed by mass spectroscopy and
1H NMR using a Bruker Avance III, with cryoprobe operating at
600 MHz. High-resolution mass spectroscopy (HRMS) was
conducted on a Micromass Q-TOF I for ESI measurements and
a Kratos Concept 1S High Resolution Mass Spectrometer for EI
measurements (John L. Holmes Mass Spectroscopy Facility).
(E)-3,4,5,6,7,8,9,10-octahydro-1H-
benzo[c][1]oxacyclotetradecin-1-one (4). To 105 mL dry toluene
was added 120 mg 3 (0.42 mmol) under argon, to this stirred
solution 18 mg of Grubbs 2nd Gen. catalyst (0.02 mmol, 5 mol%)
was added. The reaction was stirred at 80˚C for 24 hours. At
completion the reaction was concentrated and purified by column
chromatography (95:5 Hexanes:EtOAc), yielding 96 mg (89%) of the
title compound as a colorless oil. Rf = 0.78 (9:1 hexanes:EtOAc) IR
(NaCl) νmax = 2930, 2853, 1705, 1200, 1254 cm-1 1H NMR (400 MHz,
CDCl3) δ 7.82 (dd, J = 7.8, 1.1 Hz, 1H), 7.48 (dd, J = 4.3, 3.6 Hz, 1H),
7.41 (ddd, J = 7.9, 7.3, 1.0 Hz, 1H), 7.26 (dt, J = 5.6, 2.9 Hz, 1H), 6.91
(d, J = 15.7 Hz, 1H), 5.93 (dt, J = 15.6, 7.1 Hz, 1H), 4.36 – 4.32 (m,
2H), 2.28 (ddd, J = 12.1, 7.2, 1.4 Hz, 2H), 1.79 – 1.69 (m, 2H), 1.57 –
1.31 (m, 10H) 13C NMR (100 MHz, CDCl3) δ 169.16, 138.35, 133.24,
131.65, 130.55, 130.10, 129.43, 127.33, 126.67, 65.49, 30.72, 27.19,
26.65, 26.56, 24.15, 23.89, 23.21. HRMS (+EI) : calcd for C17H22O2
(M) 258.1620, obsd 258.1618.
(E)-S-(2-acetamidoethyl)
2-(8-hydroxyoct-1-en-1-
yl)benzothioate (7). In 2 mL of dry DCM 86 mg of S3 (0.346 mmol)
was added with stirring. To this mixture 40.5 μL of HSNAC (0.381
mmol, 1.1 eq.), 87 mg of EDC (0.450 mmol, 1.3 eq.), and 4 mg
DMAP (0.035 mmol, 0.1 eq.) were added under an argon
atmosphere. The reaction mixture was stirred overnight at room
temperature. At completion the reaction was quenched by the
addition of sat. NH4Cl, the organic layer was separated and the
remaining aqueous layer was extracted 3x 10 mL DCM. The
combined organic fractions were pooled, dried with Na2SO4 and
concentrated in vacuo and purified by column chromatography (6:4
Acetone:Hexanes) to yield 80 mg (66%) of 7 as a slightly yellow oil.
Rf = 0.44 (1:1 hexanes:acetone) IR (NaCl) νmax = 3282(br), 3066,
2931, 2858, 1653, 1191 cm-1 1H NMR (400 MHz, CDCl3) δ 7.71 (dd, J
= 7.8, 0.9 Hz, 1H), 7.53 (d, J = 6.6 Hz, 1H), 7.43 (dd, J = 10.8, 4.3 Hz,
1H), 7.30 – 7.22 (m, 2H), 6.75 (d, J = 15.8 Hz, 1H), 6.31 (s, 1H), 6.14
(dt, J = 15.7, 6.9 Hz, 1H), 3.65 (t, J = 6.5 Hz, 2H), 3.56 – 3.47 (m, 2H),
3.18 (t, J = 6.5 Hz, 2H), 2.27 – 2.17 (m, 2H), 1.99 (s, 3H), 1.62 – 1.33
(m, 8H) 13C NMR (100 MHz, CDCl3) δ 194.77, 170.44, 136.72, 135.70,
134.55, 132.02, 128.44, 127.46, 127.08, 126.67, 62.89, 39.69, 32.84,
32.79, 29.25, 28.84, 28.67, 25.45, 23.23. HRMS (+EI) : calcd for
(E)-2-(10-hydroxydec-1-en-1-yl)benzoic acid (5). In a 10 mL
round bottom 96 mg 4 (0.371 mmol) was dissolved in 4:1:3
methanol:water:THF (8 mL total) and to this 156 mg of LiOH (3.71
mmol, 10 eq.) was added. The reaction was stirred over night at
50˚C. At completion the reaction was diluted with water and the pH
was adjusted to 2 using 10% HCl. This was extracted 3x 10 mL with
EtOAc and the organic fractions were combined, dried over Na2SO4,
and concentrated in vacuo. This yielded 83 mg seco-acid 5 (80%) as
C
15H19O2 (M-SC2H4NHCOCH3) 231.1385, obsd 231.1365.
(E)-S-(2-acetamidoethyl) 2-(12-hydroxydodec-1-en-1-
yl)benzothioate (8). In a 10 mL round bottom flask was combined
200 mg S6 (0.33 mmol, 1 eq.), 52 μL HSNAC (0.5 mmol, 1.5 eq.), 96
mg EDC (0.5 mmol, 1.5 eq.), and 4 mg DMAP (0.033 mmol, 0.1 eq.)
in 2 mL anhydrous DCM. The reaction was stirred under argon,
overnight at room temperature. The reaction was quenched by the
addition of sat. NH4Cl, and the organic layer was removed. The
aqueous remainder was extracted with DCM. The combined organic
fractions were washed with brine, dried over Na2SO4, and
concentrated. The compounds was purified by column
chromatography (100% EtOAc) yielding 76 mg of 8 (30%) as a thick
oil. Rf = 0.48 (1:1 hexanes:acetone) IR (NaCl) νmax = 3755, 3285 (br),
2928, 2856, 1662, 1189, 1098 cm-1 1H NMR (400 MHz, CDCl3) δ 7.70
(ddd, J = 7.8, 1.4, 0.6 Hz, 1 H), 7.54 (ddd, J = 7.9, 0.7, 0.5 Hz, 1 H),
7.42 (dddd, J = 7.8, 7.4, 1.4, 0.6 Hz, 1 H), 7.25 (ddd, J = 7.7, 7.5, 1.3
Hz, 1 H), 6.77 (d, J = 15.7 Hz, 1 H), 6.17 (dt, J = 15.7, 7.0 Hz, 1 H),
5.92 (bs, 1 H), 3.62 (t, J = 6.6 Hz, 2 H), 3.53 (dt, J = 6.5, 6.2 Hz, 2 H),
3.19 (t, J = 6.2 Hz, 2 H), 2.25-2.15 (m, 2 H), 1.97 (s, 3 H), 1.64-1.49
(m, 4 H), 1.49-1.39 (m, 2 H), 1.38-1.24 (m, 10 H) 13C NMR (75 MHz,
CDCl3) δ 194.8 170.3, 136.7, 135.7, 135.0, 132.0, 128.4, 127.0,
127.0, 126.6, 63.1, 39.8, 33.2, 32.8, 31.6, 29.5, 29.5, 29.4, 29.4,
29.2, 25.7, 22.7, 14.1 HRMS (+EI) : calcd for C23H35NO3S (M)
405.2338, obsd 405.2356.
1
a clear oil. Rf = 0.22 (1:1 EtOAc:hexanes) H NMR (400 MHz, CDCl3)
δ 7.94 (dd, J = 7.9, 0.9 Hz, 1H), 7.52 (d, J = 7.4 Hz, 1H), 7.48 – 7.43
(m, 1H), 7.27 (dd, J = 10.3, 3.6 Hz, 1H), 7.18 (d, J = 15.8 Hz, 1H), 6.08
(dt, J = 15.6, 7.0 Hz, 1H), 3.66 (t, J = 6.4 Hz, 2H), 2.28 – 2.20 (m, 2H),
1.61 – 1.31 (m, 10H) 13C NMR (100 MHz, CDCl3) δ 171.67, 140.45,
134.22, 132.59, 131.03, 128.94, 127.52, 127.26, 126.54, 63.03,
32.81, 32.45, 29.18, 29.08, 28.79, 28.53, 25.46. HRMS (+EI) : calcd
for C17H24O3 (M) 276.1725, obsd 276.1719.
(E)-S-(2-acetamidoethyl)
2-(10-hydroxydec-1-en-1-
yl)benzothioate (6). In 4 mL of dry DCM, 101 mg of 5 (0.365 mmol)
was added with stirring. To this mixture 42.6 μL of HSNAC (0.401
mmol, 1.1 eq.), 91 mg of EDC (0.475 mmol, 1.3 eq.), and 4.5 mg
DMAP (0.037 mmol, 0.1 eq.) were added under an argon
atmosphere. The reaction mixture was stirred overnight at room
temperature. At completion the reaction was quenched by the
addition of sat. NH4Cl, the organic layer was separated and the
remaining aqueous layer was extracted 3x 10 mL DCM. The
combined organic fractions were pooled, dried with Na2SO4 and
concentrated in vacuo and purified by column chromatography (1:1
Acetone:Hexanes) to yield 29 mg (21%) of 6 as a slightly yellow oil.
Rf = 0.23 (1:1 hexanes:acetone) IR (NaCl) νmax = 2930, 2853, 1705,
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