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PRACTICAL SYNTHETIC PROCEDURES
HCl (60 mL) was added to the mixture. The aqueous layer was
washed with Et2O (4 15 mL), neutralized with aq 6 M NaOH, and
then extracted with Et2O (4 15 mL). The combined organic layers
were dried (Na2SO4). Concentration in vacuo and subsequent puri-
fication by column chromatography (silica gel 60 N, spherical neu-
tral) with hexane–EtOAc (5:1, v/v) as an eluent gave the
corresponding 3-aminoindole 14.
1H NMR (400 MHz, CDCl3): d = 1.23 (t, J = 7.3 Hz, 6 H), 3.44 (qt,
J = 7.3, 1.4 Hz, 4 H).
13C NMR (100 MHz, CDCl3): d = 14.1, 46.8 (t, J = 4.8 Hz), 134.59
(dm, J = 247.3 Hz), 139.5–139.7 (m), 145.4 (dm, J = 237.7 Hz).
19F NMR (373 MHz, CDCl3): d = –156.0 to –156.2 (m), –94.4 to
–94.3 (m).
HRMS (EI): m/z (M+) calcd for C9H10F4N2: 222.0780; found:
222.0784.
Representative analytical and spectral data for 14ab are provided
below. Data for other products can be found in reference 6b.
N,N-Diethyl-5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-amine
(5cb)
N,N-Diethyl-1-methanesulfonyl-2-phenylindol-3-amine (14ab)
Yield: 63 mg (0.19 mmol, 74%); orange oil.
Cu(OAc)2 (0.14 g, 0.75 mmol), 1,10-phenanthroline (0.14 g, 0.75
mmol), and LiOt-Bu (1.4 g, 18 mmol) were placed in a 100 mL two-
necked reaction flask, which was filled with N2 by using the stan-
dard Schlenk technique. 1,4-Dioxane (15 mL) was then added to the
flask, and the suspension was stirred for 15 min at r.t. Finally, a so-
lution of 2-(4-methoxyphenyl)-1,3,4-oxadiazole (4c; 1.6 g, 9.0
mmol) and O-benzoyl-N,N-diethylhydroxylamine (2b; 1.4 g, 7.5
mmol) in 1,4-dioxane (30 mL) was added dropwise. The solution
was stirred at r.t. for additional 5 h. The resulting mixture was
quenched with H2O (100 mL). The mixture was extracted with
EtOAc (4 20 mL), and the combined organic layers were dried
(Na2SO4). Concentration in vacuo and subsequent column chroma-
tography (silica gel 60 N, spherical neutral) with hexane–EtOAc
(1:2, v/v) as an eluent gave 5cb as a colorless oil; yield: 1.4 g (5.7
mmol, 76%).
1H NMR (400 MHz, CDCl3): d = 1.27 (t, J = 7.3 Hz, 6 H), 3.51 (q,
J = 7.3 Hz, 4 H), 3.85 (s, 3 H), 6.95 (d, J = 8.7 Hz, 2 H), 7.84 (d,
J = 8.7 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 13.3, 43.4, 55.5, 114.3, 117.7,
127.4, 158.8, 161.3, 163.7.
HRMS (EI): m/z (M+) calcd for C13H17N3O2: 247.1321; found:
247.1320.
1H NMR (400 MHz, CDCl3): d = 0.91 (t, J = 7.3 Hz, 6 H), 2.76 (s,
3 H), 3.01 (q, J = 7.3 Hz, 4 H), 7.29–7.49 (m, 7 H), 7.69 (d, J = 8.3
Hz, 1 H), 8.14 (d, J = 8.3 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 14.1, 39.7, 48.1, 116.1, 120.5,
124.0, 125.2, 127.6, 128.7, 129.7, 131.6, 131.8, 133.0, 134.8, 136.5.
HRMS (EI): m/z (M+) calcd for C19H22N2O2S: 342.1402; found:
342.1400.
Gram-Scale Syntheses (Scheme 1)
4-(Diethylamino)-2,3,5,6-tetrafluorobenzonitrile (3cb)
Cu(OAc)2 (0.14 g, 0.75 mmol), 1,10-phenanthroline (0.14 g, 0.75
mmol), and LiOt-Bu (1.4 g, 18 mmol) were placed in a 100 mL two-
necked reaction flask, which was filled with N2 by using the stan-
dard Schlenk technique. 1,4-Dioxane (15 mL) was then added to the
flask, and the suspension was stirred for 15 min at r.t. Finally, a so-
lution of 2,3,5,6-tetrafluorobenzonitrile (1c; 1.6 g, 9.0 mmol) and
O-benzoyl-N,N-diethylhydroxylamine (2b; 1.4 g, 7.5 mmol) in 1,4-
dioxane (30 mL) was added dropwise. The solution was stirred at
r.t. for additional 4 h. The resulting mixture was quenched with H2O
(100 mL). The mixture was extracted with EtOAc (4 20 mL), and
the combined organic layers were dried (Na2SO4). Concentration in
vacuo and subsequent column chromatography (silica gel 60 N,
spherical neutral) with hexane–EtOAc (40:1, v/v) as an eluent gave
3cb as a white solid; yield: 1.4 g (5.5 mmol, 74%); mp 48–49 °C.
N,N-Diethylbenzoxazol-2-amine (7)
Cu(OAc)2 (0.22 g, 1.2 mmol), 1,10-phenanthroline (0.22 g, 1.2
mmol), and LiOt-Bu (2.3 g, 29 mmol) were placed in a 100 mL two-
necked reaction flask, which was filled with N2 by using the stan-
dard Schlenk technique. 1,4-Dioxane (24 mL) was then added to the
flask, and the suspension was stirred for 15 min at r.t. Finally, a so-
lution of benzoxazole (6; 1.7 g, 14 mmol) and O-benzoyl-N,N-di-
ethylhydroxylamine (2b; 2.3 g, 12 mmol) in 1,4-dioxane (48 mL)
was added dropwise. The solution was stirred at r.t. for additional
10 h. The resulting mixture was quenched with H2O (100 mL). The
mixture was extracted with Et2O (4 20 mL), and the combined or-
ganic layers was dried (Na2SO4). Concentration in vacuo and sub-
sequent column chromatography (silica gel 60 N, spherical neutral)
with hexane–EtOAc (5:1, v/v) as an eluent gave 7 as a colorless oil;
yield: 0.93 g (4.9 mmol, 40%).
1H NMR (400 MHz, CDCl3): d = 1.28 (t, J = 7.3 Hz, 6 H), 3.59 (q,
J = 7.3 Hz, 4 H), 6.98 (t, J = 7.8 Hz, 1 H), 7.14 (t, J = 7.8 Hz, 1 H),
7.24 (d, J = 7.8 Hz, 1 H), 7.35 (d, J = 7.8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 13.7, 43.1, 108.7, 116.0, 120.1,
124.0, 143.9, 149.0, 162.4.
1H NMR (400 MHz, CDCl3): d = 1.19 (t, J = 7.3 Hz, 6 H), 3.39 (q,
J = 7.3 Hz, 4 H).
13C NMR (100 MHz, CDCl3): d = 13.9, 47.0 (t, J = 4.8 Hz), 82.7
(tm, J = 8.2 Hz), 109.0 (t, J = 3.8 Hz), 135.5 (tt, J = 10.5, 2.9 Hz),
140.8 (dm, J = 249.2 Hz), 148.4 (dm, J = 251.1 Hz).
19F NMR (373 MHz, CDCl3): d = –149.9 (d, J = 17.4 Hz), –135.1
(d, J = 17.4 Hz).
HRMS (EI): m/z (M+) calcd for C11H10F4N2: 246.0780; found:
246.0777.
N,N-Diethyl-2,3,5,6-tetrafluoropyridin-4-amine (3fb)
Cu(OAc)2 (0.14 g, 0.75 mmol), 1,10-phenanthroline (0.14 g, 0.75
mmol), and LiOt-Bu (1.4 g, 18 mmol) were placed in a 100 mL two-
necked reaction flask, which was filled with N2 by using the stan-
dard Schlenk technique. 1,4-Dioxane (15 mL) was then added to the
flask, and the suspension was stirred for 15 min at r.t. Finally, a so-
lution of 2,3,5,6-tetrafluoropyridine (1f; 1.4 g, 9.0 mmol) and O-
benzoyl-N,N-diethylhydroxylamine (2b; 1.4 g, 7.5 mmol) in 1,4-di-
oxane (30 mL) was added dropwise. The solution was stirred at r.t.
for additional 4 h. The resulting mixture was quenched with H2O
(100 mL). The mixture was extracted with Et2O (4 20 mL), and
the combined organic layers were dried (Na2SO4). Concentration in
vacuo and subsequent column chromatography (silica gel 60 N,
spherical neutral) with hexane–EtOAc (40:1, v/v) as an eluent gave
3fb as a colorless oil; yield: 1.6 g (7.3 mmol, 98%).
HRMS (EI): m/z (M+) calcd for C11H14N2O: 190.1106; found:
190.1101.
Acknowledgment
This work was supported by Grants-in-Aid for Scientific Research
from MEXT and JSPS, Japan. K. H. acknowledges Kansai Research
Foundation for the Promotion of Science.
Synthesis 2012, 44, 1792–1797
© Thieme Stuttgart · New York