Synthesis of Octane-1,8-Diol Ester Compound

In a 300-mL two-necked round-bottomed
flask equipped
with a magnetic stirring bar, a rubber septum and an argon balloon,
NaH (60% dispersion in mineral oil, 6.44 g, 161 mmol), and THF (60
mL) were added, respectively. The reaction mixture was stirred, and
octane-1,8-diol (3.92 g, 26.8 mmol) in THF (30 mL) was added. The
reaction mixture was warmed to reflux and stirred for 12 h. Then,
the reaction mixture was cooled to 0 °C and 2-bromohexanoic acid 5a (7.91 mL, 56.3 mmol) was added slowly to this reaction
mixture. The reaction mixture was warmed to reflux and stirred for
48 h. After the reaction, the reaction mixture was cooled to 0 °C
and ice water (100 mL) was added to quench the reaction. The whole
mixture was extracted with 1 M NaOH (5 × 10 mL). Then, the pH
was adjusted to 1 with 2 M H₂SO₄ solution. The
whole mixture was extracted with diethyl ether (5 × 10 mL). The
combined organic phases were washed with H₂O (20 mL), dried
(with Na₂SO₄), and concentrated in vacuo to
give a crude product. The crude product was purified by flash column
chromatography on silica gel (n-hexane/ethyl acetate/acetic
acid = 7:3:0.1) to give the title compound 7c (5.78 g).
In a 100-mL one-necked round-bottomed flask equipped with a magnetic
stirring bar and a rubber septum, product 7c, EtOH (15
mL), and MeSNa aq (15 wt %, 15 mL) were added, respectively. The reaction
mixture was warmed to 40 °C and stirred for 24 h. After the reaction,
the reaction mixture was concentrated in vacuo, and the pH was adjusted
to 1 with 2 M H₂SO₄ solution. The whole mixture
was extracted with diethyl ether (5 × 10 mL). The combined organic
phases were washed with H₂O (20 mL), dried (with Na₂SO₄), and concentrated in vacuo to give the title
compound 7c (5.41 g, 54%). Yellow oil; ¹H
NMR (500 MHz, CDCl₃) δ 3.86 (dd, J = 4.8, 7.1 Hz, 2H), 3.59 (dt, J = 6.5, 9.4 Hz,
2H), 3.49–3.37 (m, 2H), 1.82–1.72 (m, 4H), 1.65–1.56
(m, 4H), 1.46–1.29 (m, 16H), 0.91 (t, J =
7.0 Hz, 6H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 177.5, 78.8, 71.0, 32.2, 29.5, 29.1, 27.1, 25.8,
22.3, 13.8; IR (neat) 3424, 2952, 2866, 1643, 1459, 1383, 1279, 1207,
1128, 926, cm^–1; HRMS (EI) m/z: [M-CHO₂]⁺ calcd for C₁₉H₃₇O₄ 329.2692, found 329.2692.