in methanol (10 mL) and then placed in a syringe, which was
then attached to a syringe pump. The methanol solution was fed
into a stainless steel column (inner volume: 0.53 mL, 4.0 mm
i.d. © 50 mm) filled in HO-SAS (334 mg) with a flow rate of
0.177 mL¢min¹1. The column was immersed into an oil bath
(110 °C). A back-pressure regulator (75 psi) was connected.
The reaction mixture was collected from the outlet. The reac-
tion mixture eluted during the first 10 min was discarded. The
reaction mixture was collected during 3 min and added n-
decane as an internal standard for GC analysis. The following
portion was collected for a 30 min period in a glass flask, and
solvent was evaporated. The crude mixture was purified by
flash column chromatography on SiO2 (hexane/ethyl acetate =
5/1) to give 3a (1.13 g, 99%).
Methyl (2E,4E)-Hexa-2,4-dienoate (3f):25 Colorless oil,
(0.244 g, 91% yield, 60 min collected), H NMR (CDCl3, 400
1
MHz) δ 7.19 (dd, J = 15.6, 9.6 Hz, 1H), 6.12-6.05 (m, 2H),
5.76 (d, J = 15.6 Hz, 1H), 3.66 (s, 3H), 1.78 (d, J = 5.7 Hz,
3H); 13C NMR (CDCl3, 100 MHz) δ 167.7, 145.2, 139.4, 129.8,
118.6, 51.4, 18.6.
Methyl 2-Ethylhexanoate (3g):26 Colorless oil, (0.262 g,
74% yield, 60 min collected), 1H NMR (CDCl3, 400 MHz)
δ 3.60 (s, 3H), 2.20 (m, 1H), 1.60-1.34 (m, 4H), 1.31-1.13 (m,
4HH), 0.81 (t, J = 7.3 Hz, 6H); 13C NMR (CDCl3, 100 MHz)
δ 176.9, 51.2, 47.2, 31.8, 29.6, 25.5, 22.6, 13.9, 11.8.
Methyl 4-(Tert-butyl)benzoate (3h):27
Colorless oil,
1
(0.387 g, 90% yield, 60 min collected), H NMR (CDCl3, 400
MHz) δ 7.97 (d, J = 8.8 Hz, 2H), 7.45 (d, J = 8.8 Hz, 2H), 3.90
(s, 3H), 1.34 (s, 9H); 13C NMR (CDCl3, 100 MHz) δ 167.3,
156.7, 129.6, 127.5, 125.5, 52.1, 35.2, 31.3.
Procedure for Scalable Flow Esterification (Scheme 4).
Lauric acid (1a) (20.03 g, 100 mmol) was dissolved in meth-
anol (100 mL), and pumped (flow rate = 0.18 mL/min) by
HPLC pump. The methanol solution was fed into a stainless
steel column (inner volume: 0.53 mL, 4.0 mm i.d. © 50 mm)
filled in HO-SAS (331 mg). The column was immersed into
an oil bath (110 °C). A back-pressure regulator (75 psi) was
connected. The reaction mixture was collected from the outlet.
The reaction mixture eluted during the first 10 min was dis-
carded. The reaction mixture was collected over 3 min and
n-decane added as an internal standard and analyzed by GC.
The following portion was collected for a 390 min period in a
glass flask. After 90, 200, and 360 minutes from the start of
collection, each portion was collected for 1 minute, in which n-
decane was added and analyzed by GC. All corrected reaction
mixture was evaporated and the residue was filtered through
silica-gel pad and washed with AcOEt. Concentration of the
solution gave 3a (14.9 g, 99%, 69.4 mmol).
Methyl 2-(1,3-Dioxoisoindolin-2-yl)acetate (3i):28 White
solid, mp 112-114 °C, (1.20 g, 94% yield, 30 min collected),
1H NMR (CDCl3, 400 MHz) δ 7.90-7.87 (m, 2H), 7.77-7.73
(m, 2H), 4.45 (s, 2H), 3.77 (s, 3H); 13C NMR (CDCl3, 100
MHz) δ 167.9, 167.6, 134.4, 132.1, 123.8, 52.8, 38.9.
Methyl 12-Hydroxyoctadecanoate (3j):29
White solid,
1
mp 53-55 °C, (0.589 g, 99% yield, 26 min collected), H NMR
(CDCl3, 400 MHz) δ 3.67 (s, 3H), 3.58 (br, 1H), 2.30 (t, J =
7.6 Hz, 2H), 1.70-1.25 (m, 28H), 0.88 (t, J = 7.6 Hz, 3H);
13C NMR (CDCl3, 100 MHz) δ 174.5, 72.2, 51.6, 37.6, 34.3,
32.0, 29.8, 29.7, 29.6, 29.5, 29.4, 29.3, 25.8, 25.1, 22.8, 14.2.
3α,7β-Dihydroxy-5β-cholan-24-oic Acid Methyl Ester
(3k):30 White solid, mp 60-61 °C, (1.05 g, 90% yield, 30
min collected), 1H NMR (CDCl3, 400 MHz) δ 3.65 (s, 3H),
3.60-3.54 (m, 2H), 2.38-2.31 (m, 1H), 2.25-2.17 (m, 1H),
2.03-1.73 (m, 9H), 1.69-1.54 (m, 4H), 1.53-0.93 (m, 12H),
0.92 (t, J = 5.6 Hz, 6H), 0.66 (s, 3H); 13C NMR (CDCl3,
100 MHz) δ 174.9, 71.5, 71.5, 55.9, 55.0, 51.6, 43.9, 42.6,
40.3, 39.3, 37.4, 37.0, 35.4, 35.0, 34.2, 31.2, 31.1, 30.4, 28.7,
27.0, 23.5, 21.3, 18.5, 12.3.
Methyl Laurate (3a):20 Colorless oil, (1.13 g, 99% yield,
1
30 min collected), H NMR (CDCl3, 400 MHz) δ 3.66 (s, 3H),
2.30 (t, J = 8.0 Hz, 2H), 1.65-1.58 (m, 2H), 1.28-1.25 (m,
16H), 0.88 (t, J = 6.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
δ 174.5, 51.6, 34.3, 32.1, 29.7, 29.6, 29.5, 29.4, 29.3, 25.1,
22.8, 14.3.
Ethyl Laurate (3l):20 Colorless oil, (0.880 g, 81% yield,
1
30 min collected), H NMR (CDCl3, 400 MHz) δ 4.12 (q, J =
Methyl Octanoate (3b):21 Colorless oil, (0.828 g, 96%
yield, 30 min collected), 1H NMR (CDCl3, 400 MHz) δ 3.66 (s,
3H), 2.29 (t, J = 8.0 Hz, 2H), 1.61 (m, 2H), 1.32-1.20 (m, 8H),
0.87 (t, J = 8.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 174.5,
51.6, 34.2, 31.8, 29.2, 29.0, 25.1, 22.7, 14.2.
7.2 Hz, 2H), 2.28 (t, J = 7.6 Hz, 2H), 1.62-1.59 (m, 2H), 1.28-
1.23 (m, 19H), 0.87 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3,
100 MHz) δ 174.1, 60.3, 34.5, 32.1, 29.7, 29.6, 29.5, 29.4,
29.3, 25.1, 22.8, 14.4, 14.3.
Isopropyl Laurate (3m):20 Colorless oil, (0.0486 g, 76%
1
Methyl Stearate (3c):22
White solid, mp 39-40 °C,
yield, 20 min collected), H NMR (CDCl3, 400 MHz) δ 5.00
1
(0.622 g, 97% yield, 23 min collected), H NMR (CDCl3, 400
MHz) δ 3.66 (s, 3H), 2.30 (t, J = 7.6 Hz, 2H), 1.62-1.59 (m,
2H), 1.28-1.23 (m, 28H), 0.88 (t, J = 6.8 Hz, 3H); 13C NMR
(CDCl3) δ 174.5, 51.6, 34.3, 32.1, 29.8, 29.6, 29.5, 29.4, 29.3,
25.1, 22.8, 14.3.
(sept, J = 6.3 Hz, 1H), 2.25 (t, J = 7.5 Hz, 2H), 1.65-1.56
(m, 2H), 1.23 (d, J = 6.3 Hz, 6H), 1.08-1.33 (m, 16H), 0.88
(t, J = 6.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 173.5, 67.3,
34.7, 31.9, 29.6, 29.5, 29.3, 29.1, 25.0, 22.7, 21.8, 14.1.
3-Methylbutyl Laurate (3n):31 Colorless oil, (0.582 g,
83% yield, 15 min collected), 1H NMR (CDCl3, 400 MHz)
δ 4.09 (t, J = 6.8 Hz, 2H), 2.28 (t, J = 7.2 Hz, 2H), 1.71-1.57
(m, 3H), 1.51 (q, J = 6.8 Hz, 2H), 1.35-1.21 (m, 16H), 0.93-
0.85 (m, 9H); 13C NMR (CDCl3, 100 MHz) δ 174.2, 63.0, 37.5,
34.6, 32.1, 29.7, 29.6, 29.5, 29.4, 29.3, 25.2, 22.8, 22.6, 14.3.
Decyl Acetate (3o):16a Colorless oil, (0.970 g, 87% yield,
Methyl Pent-4-enoate (3d):23
Colorless oil, (0.545 g,
85% yield, 30 min collected), 1H NMR (CDCl3, 400 MHz)
δ 5.80-5.72 (m, 1H), 5.02-4.92 (m, 2H), 3.62 (s, 3H), 2.38-
2.30 (m, 4H); 13C NMR (CDCl3, 100 MHz) δ 173.5, 136.7,
115.5, 51.5, 33.3, 28.9.
Methyl 5-Bromopentanoate (3e):24 Brownish oil, (1.05 g,
99% yield, 30 min collected), 1H NMR (CDCl3, 400 MHz)
δ 3.67 (s, 3H), 3.41 (t, J = 6.3 Hz, 2H), 2.35 (t, J = 7.4 Hz,
2H), 1.91-1.86 (m, 2H), 1.81-1.76 (m, 2H); 13C NMR (CDCl3,
100 MHz) δ 173.8, 51.8, 33.2, 23.6.
1
30 min collected), H NMR (CDCl3, 400 MHz) δ 4.06 (t, J =
6.8 Hz, 2H), 2.04 (s, 3H), 1.58-1.64 (m, 2H), 1.38-1.28 (m,
14H), 0.87 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
δ 171.4, 64.8, 32.0, 29.7, 29.4, 28.7, 26.1, 22.8, 21.2, 14.3.
© 2017 The Chemical Society of Japan