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G. Kobayashi et al.
PAPER
pressure. The residue was purified by column chromatography on
silica gel (EtOAc–hexane, 1:1) to yield 13 (913 g, 50%) as a color-
less oil.
1H NMR (600 MHz, CDCl3): d (major) = 8.23 (1 H, d, J = 13 Hz),
5.60 (1 H, br s), 3.54 (2 H, t, J = 7.3 Hz), 1.77 (2 H, quint, J = 7.3
Hz), 1.52–1.47 (2 H, m), 1.45–1.38 (2 H, m), 1.36–1.23 (18 H, m);
d (minor) = 8.05 (1 H, s), 5.14 (1 H, br s), 3.54 (2 H, t, J = 7.3 Hz),
1.77 (2 H, quint, J = 7.3 Hz), 1.52–1.47 (2 H, m), 1.45–1.38 (2 H,
m), 1.36–1.23 (18 H, m).
13C NMR (150.8 MHz, CDCl3): d (major) = 160.4, 52.8, 45.2, 43.8,
40.6, 32.6, 29.8, 29.5, 29.4, 28.8, 28.7, 27.0, 23.8; d (minor) =
162.9, 54.0, 45.2, 43.8, 40.6, 32.6, 29.9, 29.6, 29.4, 28.8, 28.7, 26.8,
24.0. HRMS (ESI): m/z (M + Na)+ calcd for C14H28ClNO + Na:
284.1757; found: 248.1757.
IR (neat): 3354 (br), 3415 (br), 2877, 2754, 1738, 1655, 1599, 1308,
1211, 1120, 1020 cm–1.
1H NMR (600 MHz, CDCl3): d = 7.79 (2 H, d, J = 8.5 Hz), 7.34 (2
H, d, J = 8.5 Hz), 4.02 (2 H, t, J = 6.8 Hz), 2.45 (3 H, s), 1.63 (2 H,
quint, J = 6.8 Hz), 1.47–1.43 (2 H, m), 1.36–1.19 (21 H, m).
13C NMR (150.8 MHz, CDCl3): d = 144.5, 133.2, 129.7, 127.8,
70.9, 70.6, 43.9, 30.1, 29.5, 29.3, 29.2, 29.1, 28.8, 28.7, 25.2, 24.2,
21.5.
HRMS (ESI): m/z (M + Na)+ calcd for C20H34O4S + Na: 393.2075;
N-(1,1-Dimethyl-10-tosyloxyundecyl)formamide (14)
TsCl (4.50 g, 23.6 mmol) was added to a solution of formamide 9
(2.61 g, 10.7 mmol) in pyridine (8 mL). After stirring the reaction
mixture at r.t. for 4 h, brine (30 mL) was added, and the resultant
mixture was extracted with EtOAc (300 mL). The combined ex-
tracts were washed with aq 1 M HCl (100 mL), sat. aq NaHCO3 (50
mL) and brine (50 mL), dried (MgSO4), and concentrated under re-
duced pressure. The residue (3.1 g) was mixed with 50% AcOH (20
mL) and the reaction mixture was stirred at r.t. for 16 h. Brine (30
mL) was added to the mixture, and the resultant mixture was ex-
tracted with EtOAc (300 mL). The combined extracts were washed
with sat. aq NaHCO3 (100 mL) and brine (50 mL), dried (MgSO4),
and concentrated under reduced pressure. The residue was purified
by column chromatography on silica gel (EtOAc–hexane, 1:1) to
yield 14 (2.05 g, 48%) as a colorless oil.
found: 393.2075.
N-(11-Fluoro-1,1-dimethylundecyl)formamide (5h)
KF (6.20 g, mmol) was added to a solution of tosylate 13 (1.51 g,
4.08 mmol) in ethylene glycol (30 mL). After stirring the reaction
mixture at r.t. for 7 d, brine (100 mL) was added, and the resultant
mixture was extracted with EtOAc (250 mL). The combined ex-
tracts were washed with H2O (100 mL) and brine (50 mL), dried
(MgSO4), and concentrated under reduced pressure. The residue
was purified by column chromatography on silica gel (EtOAc–
hexane, 1:4) to yield the corresponding alcohol (381 mg, 43%) as a
colorless oil. TMSCN (200 mL, 1.62 mmol) and H2SO4 (116 mL
1.62 mmol) were successively added to a solution of the above al-
cohol (381 mg, 1.74 mmol) in AcOH (200 mL) at 0 °C. After stirring
the reaction mixture at r.t. for 2 d, aq 10% NaOH (50 mL) was add-
ed at 0 °C, and the resultant mixture was extracted with EtOAc (200
mL). The combined extracts were washed with H2O (50 mL) and
brine (50 mL), dried (MgSO4), and concentrated under reduced
pressure. The residue was purified by column chromatography on
silica gel (EtOAc–hexane, 1:1) to yield 5h (212 mg, 89%) as a col-
orless oil.
IR (neat): 3302 (br), 3053, 2970, 2929, 2854, 2752, 1738, 1689,
1385, 1242, 1047 cm–1.
1H NMR (600 MHz, CDCl3): d (major) = 8.23 (1 H, d, J = 12.5 Hz),
7.79 (2 H, d, J = 8.1 Hz), 7.35 (2 H, d, J = 8.1 Hz), 5.61 (1 H, br s),
4.02 (2 H, t, J = 6.6 Hz), 2.45 (3 H, s), 1.71–1.66 (2 H, m), 1.66–
1.59 (2 H, m), 1.35–1.19 (20 H, m); d (minor) = 8.05 (1 H, d, J = 1.5
Hz), 7.79 (2 H, d, J = 8.1 Hz), 7.35 (2 H, d, J = 8.1 Hz), 5.17 (1 H,
br s), 4.02 (2 H, t, J = 6.6 Hz), 2.45 (3 H, s), 1.71–1.66 (2 H, m),
1.66–1.59 (2 H, m), 1.35–1.19 (20 H, m).
IR (neat): 3292 (br), 2924, 2854, 2752, 1684, 1541, 1456, 1387,
1263, 1219, 1049 cm–1.
1H NMR (600 MHz, CDCl3): d (major) = 8.22 (1 H, d, J = 12.4 Hz),
5.63 (1 H, br s), 4.44 (2 H, dt, J = 47.6, 6.6 Hz), 1.74–1.65 (2 H, m),
1.52–1.22 (22 H, m); d (minor) = 8.04 (1 H, d, J = 2.2 Hz), 5.14 (1
H, br s), 4.44 (2 H, dt, J = 47.6, 6.6 Hz), 1.74–1.65 (2 H, m), 1.52–
1.22 (22 H, m).
13C NMR (150.8 MHz, CDCl3): d (major) = 160.4, 144.6, 133.1,
129.7, 127.8, 70.6, 52.7, 43.6, 29.8, 29.4, 29.2, 28.8, 28.7, 28.6,
27.0, 25.2, 23.9, 21.6; d (minor) = 163.0, 144.6, 133.1, 129.7, 127.8,
70.7, 53.9, 43.6, 29.8, 29.4, 29.2, 28.8, 28.7, 28.6, 27.0, 25.2, 23.9,
21.6.
13C NMR (150.8 MHz, CDCl3): d (major) = 163.1, 83.8 (d,
J = 163.8 Hz), 62.4, 40.3, 30.0, 29.7, 29.2, 28.9, 26.7, 24.9, 24.8,
23.7, 23.5; d (minor) = 160.4, 83.8 (d, J = 163.8 Hz), 53.5, 43.3,
30.2, 29.6, 29.3, 29.2, 28.2, 24.9, 24.8, 23.7, 23.5.
HRMS (ESI): m/z (M + Na)+ calcd for C14H28FNO + Na: 268.2053;
found: 268.2054.
HRMS (ESI): m/z (M + Na)+ calcd for C21H35NO4S + Na: 420.2184;
found: 420.2183.
N-(11-Iodo-1,1-dimethylundecyl)formamide (5j)
KI (647 mg, 3.90 mmol) was added to a solution of tosylate 14 (502
mg, 1.26 mmol) in MeCN (10 mL). After stirring the reaction mix-
ture under reflux for 72 h, brine (100 mL) was added, and the result-
ant mixture was extracted with EtOAc (300 mL). The combined
extracts were washed with H2O (50 mL) and brine (50 mL), dried
(MgSO4), and concentrated under reduced pressure. The residue
was purified by column chromatography on silica gel (EtOAc–
hexane, 1:3) to yield formamide 5j (404 mg, 91%) as yellow oil.
N-(11-Chloro-1,1-dimethylundecyl)formamide (5i)
TsCl (4.50 g, 23.6 mmol) was added to a solution of formamide 9
(2.61 g, 10.7 mmol) in pyridine (8 mL). After stirring the reaction
mixture at r.t. for 24 h, brine (30 mL) was added, and the resultant
mixture was extracted with EtOAc (300 mL). The combined ex-
tracts were washed with aq 1 M HCl (50 mL), sat. aq NaHCO3 (50
mL) and brine (50 mL), dried (MgSO4), and concentrated under re-
duced pressure. The residue (3.1 g) was mixed with 50% AcOH (20
mL), and the reaction mixture was stirred at r.t. for 16 h. Brine (30
mL) was added, and the resultant mixture was extracted with EtOAc
(300 mL). The combined extracts were washed with sat. aq
NaHCO3 (100 mL) and brine (50 mL), dried (MgSO4), and concen-
trated under reduced pressure. The residue was purified by column
chromatography on silica gel (EtOAc–hexane, 1:2) to yield the 5i
(352 mg, 12%) as a colorless oil.
IR (neat): 3291 (br), 2968, 2927, 2852, 2752, 1740, 1690, 1537,
1466, 1456, 1387, 1365, 1313, 1259, 1240, 1228, 1173, 1088, 1047
cm–1.
1H NMR (600 MHz, CDCl3): d (major) = 8.23 (1 H, d, J = 13 Hz),
5.64 (1 H, br s), 3.19 (2 H, t, J = 7.3 Hz), 1.82 (2 H, quint, J = 7.3
Hz), 1.70–1.66 (2 H, m), 1.41–1.23 (20 H, m); d (minor) = 8.05 (1
H, s), 5.15 (1 H, br s), 3.19 (2 H, t, J = 7.3 Hz), 1.82 (2 H, quint,
J = 7.3 Hz), 1.70–1.66 (2 H, m), 1.41–1.23 (20 H, m).
13C NMR (150.8 MHz, CDCl3): d (major) = 160.4, 52.8, 43.8, 33.5,
30.5, 29.9, 29.6, 29.5, 29.3, 28.7, 28.5, 27.0, 24.0, 7.4; d (minor) =
IR (neat): 3296 (br), 2968, 2929, 2854, 2754, 1740, 1685, 1539,
1466, 1387, 1365, 1311, 1173, 1047, cm–1.
Synthesis 2011, No. 20, 3225–3234 © Thieme Stuttgart · New York