Full Papers
aminoethanol (180 mL, 3.0 mmol) at room temperature for 40 h.
Upon completion, the reaction mixture was diluted with 70 mL of
water and extracted twice with 15 mL of ethyl acetate. The organic
layers were combined and extracted with 30 mL of a 1m aqueous
solution of hydrochloric acid. The organic layer was discarded, and
the aqueous layer was basified by addition of 40 mL of a 1m aque-
ous solution of sodium hydroxide, then extracted twice with 20 mL
of ethyl acetate. The combined organic layers were dried over an-
hydrous sodium sulfate, filtered, and concentrated under reduced
pressure to give the desired pure product 3ao as a viscous brown-
ish oil (98.7 mg, 0.58 mmol, 58%). 1H NMR (300 MHz, CDCl3): d=
8.08 (br. s, 1H), 7.24 (d, J=8.7 Hz, 1H), 7.16 (t, J=2.9 Hz, 1H), 6.95
(d, J=2.1 Hz, 1H), 6.71 (dd, J=8.7, 2.4 Hz, 1H), 6.44–6.46 (m, 1H),
3.88 (t, J=5.3 Hz, 2H), 3.37 (t, J=5.1 Hz, 2H), 2.88 ppm (br.s, 2H);
13C NMR (300 MHz, CDCl3): d=142.1, 130.6, 128.8, 127.7, 112.8,
111.8, 103.3, 101.9, 61.5, 47.8 ppm; IR (ATR): n˜max =3401, 2933,
1723, 1373, 1168, 1137, 843, 799 cmÀ1; ESI HRMS m/z calcd for
C10H12N2O: 177.1022 [M+H]+; found: 177.1023.
7 mL of diethyl ether. The organic layers were combined, dried
over anhydrous magnesium sulfate, filtered, and concentrated
under vacuum. The crude residue was purified by flash column
chromatography over silica gel (petroleum ether/EtOAc=90:10) to
afford the desired pure product 3aw as a yellow solid (10.5 mg,
1
0.032 mmol, 61%). M.p.: 98–1008C; H NMR (300 MHz, CDCl3): d=
7.87 (d, J=8.7 Hz, 2H), 7.52 (d, J=8.4 Hz, 2H), 7.20 (d, J=7.8 Hz,
2H), 6.62 (d, J=8.7 Hz, 2H), 3.19 (t, J=7.2 Hz, 2H), 2.40 (s, 3H),
1.68–1.58 (m, 2H), 1.46 (app. sext., J=7.4 Hz, 2H), 0.98 ppm (t, J=
7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=166.0, 152.0, 141.5, 132.8,
130.0, 129.4, 117.7, 112.8, 111.9, 110.2, 97.4, 73.7, 43.7, 32.0, 22.3,
20.8, 14.4 ppm; IR (ATR) n˜max =1652, 1520, 1472, 1182, 1166, 1033,
817, 742 cmÀ1; ESI HRMS m/z calcd for C21H21N3O: 331.1757 [M+
H]+; found: 332.1759.
15-Butylamino-2,3,5,6,8,9,11,12-octahydrobenzo[b][1,4,7,10,13]-
pentaoxacyclopentadecane 3ax: Obtained according to the gen-
eral procedure from 15-iodo-2,3,5,6,8,9,11,12-octahydrobenzo[b]
[1,4,7,10,13]pentaoxacyclopentadecane (49.8 mg, 0.013 mmol) and
butylamine (37 mL, 0.38 mmol) at room temperature for 40 h. Upon
completion, the reaction mixture was diluted with 10 mL of a 25%
aqueous solution of tetramethylammonium hydroxide (TMAOH)
and extracted twice with 5 mL of ethyl acetate. The organic layers
were combined and extracted with 10 mL of a 1m aqueous solu-
tion of hydrochloric acid. The organic layer was discarded and the
aqueous layer was basified by addition of 15 mL of a 25% aqueous
solution of TMAOH, then extracted twice with 20 mL of ethyl ace-
tate. The combined organic layers were dried over anhydrous mag-
nesium sulfate, filtered, and concentrated under reduced pressure
to afford the desired pure product 3ax as a brownish solid (28 mg,
0.083 mmol, 64%). M.p.: 61–638C; 1H NMR (300 MHz, CDCl3): d=
6.76 (d, J=8.7 Hz, 1H), 6.22 (d, J=2.4 Hz, 1H), 6.14 (dd, J=5.7,
2.6 Hz, 1H), 4.12–4.05 (m, 4H), 3.91–3.85 (m, 4H), 3.74 (br.s, 8H),
3.05 (t, J=7.1 Hz, 2H), 1.58 (app. quint., J=7.1 Hz, 2H), 1.41 (app.
sext., J=7.3 Hz, 2H), 0.94 ppm (t, J=7.4 Hz, 3H); 13C NMR (75 MHz,
CDCl3): d=150.4, 143.7, 140.9, 117.4, 104.5, 100.5, 70.7, 70.6 (2C),
2,2,2-Trifluoro-N-[2-(pyrrolidin-1-yl)phenyl]acetamide 3av: Ob-
tained according to the general procedure from 2,2,2-trifluoro-N-
(2-iodophenyl)acetamide (314.7 mg, 1.0 mmol) and pyrrolidine
(250 mL, 3.0 mmol) at room temperature for 17 h. Upon comple-
tion, the reaction mixture was diluted with 70 mL of an aqueous
solution of hydrochloric acid (pH 5) and extracted twice with
15 mL of diethyl ether. The combined organic layers were dried
over anhydrous magnesium sulfate, filtered, and concentrated
under vacuum to give the desired pure product 3av as a brown
1
solid (193 mg, 0.77 mmol, 77%). M.p.: 53–558C; H NMR (300 MHz,
CDCl3): d=9.26 (s, 1H), 8.15 (dd, J=7.8, 1.4 Hz, 1H), 7.21–7.06 (m,
3H), 3.01 (t, J=6.3 Hz, 4H), 1.96 ppm (t, J=6.3 Hz, 4H); 13C NMR
(300 MHz, CDCl3): d=155.2, 154.7, 154.2, 153.7, 141.1, 130.5, 126.2,
124.3, 121.8, 120.5, 120.0, 117.9, 114.1, 110.3, 52.7, 24.5 ppm; IR
(ATR): n˜max =1698, 1541, 1501, 1455, 1225, 1160, 754 cmÀ1; ESI
HRMS m/z calcd for C12H13F3N2O: 259.1053 [M+H]+; found:
259.1056.
1-Butyl-2-(trifluoromethyl)-benzimidazole 4a: Obtained accord-
ing to the general procedure from 2,2,2-trifluoro-N-(2-iodopheny-
l)acetamide (315.0 mg, 1.0 mmol) and butylamine (300 mL,
3.0 mmol) at room temperature for 17 h. Upon completion, the re-
action mixture was diluted with 70 mL of an aqueous solution of
hydrochloric acid (pH 5) and extracted twice with 15 mL of diethyl
ether. The combined organic layers were dried over anhydrous
magnesium sulfate, filtered, and concentrated under vacuum to
give the desired pure product 4a as a dark oil (210 mg, 0.87 mmol,
87%). This compound has been previously reported.[38]
70.5, 70.2, 69.7, 69.4, 68.5, 44.3, 31.4, 20.0, 13.6 ppm; IR (ATR) n˜max =
2929, 1518, 1454, 1251, 1236, 1200, 1136, 1087, 1056, 976, 937,
819, 789 cmÀ1; ESI HRMS m/z calcd for C18H29NO5: 340.2118 [M+
H]+; found: 340.2117.
Methyl {(S)-2-[(tert-butoxycarbonyl)amino]-3-[4-(butylamino)phe-
nyl]propanoyl}-l-phenylalaninate 3ay: Obtained according to the
general procedure from methyl {(S)-2-[(tert-butoxycarbonyl)amino]-
3-(4-iodophenyl)propanoyl}-l-phenylalaninate (552.4 mg, 1.0 mmol)
and butylamine (300 mL, 3.0 mmol) at room temperature for 17 h
in 2.5 mL of DMSO. Upon completion, the reaction mixture was di-
luted with 70 mL of water and extracted twice with 50 mL of ethyl
acetate. The organic layers were combined and washed successive-
ly with 50 mL of water and 30 mL of brine. The combined organic
layers were dried over anhydrous sodium sulfate, filtered, and con-
centrated under reduced pressure to give the desired pure product
3ay as a yellow solid (433.3 mg, 0.87 mmol, 87%). M.p.: 88–908C;
2-[2-(Trifluoromethyl)-benzimidazol-1-yl]ethan-1-ol 4b: Obtained
according to the general procedure from 2,2,2-trifluoro-N-(2-iodo-
phenyl)acetamide (314.8 mg, 1.0 mmol) and aminoethanol (300 mL,
3.0 mmol) at room temperature for 17 h. Upon completion, the re-
action mixture was diluted with 70 mL of an aqueous solution of
hydrochloric acid (pH 5) and extracted twice with 15 mL of diethyl
ether. The combined organic layers were dried over anhydrous
magnesium sulfate, filtered, and concentrated under vacuum to
give the desired pure product 4b as a brown solid (187 mg,
0.81 mmol, 81%). This compound has been previously reported.[38]
25
D
1
½a +44.5 (c=1.0, CHCl3); H NMR (300 MHz, CDCl3): d=7.45–7.43
(m, 4H), 7.25 (d, J=7.8 Hz, 4H), 6.80 (d, J=8.1 Hz, 2H), 6.56 (d, J=
7.8 Hz, 1H), 5.21 (br.s, 1H), 5.03 (q, J=6.6 Hz, 1H), 4.51 (br. s, 1H),
3.95 (s, 3H), 3.36–3.13 (m, 6H), 1.85 (app. quint., J=7.0 Hz, 2H),
1.67 (obs. app. sext., 2H), 1.67 (br. s, 9H), 1.21 ppm (t, J=7.4 Hz,
3H); 13C NMR (75 MHz, CDCl3): d=171.6, 171.5, 155.4, 147.6, 136.0,
130.2, 129.5, 129.4, 128.5, 127.1, 124.6, 112.9, 53.5, 52.3, 43.8, 38.1,
37.6, 31.7, 28.3, 20.4, 14.0 ppm; IR (ATR): n˜max =3325, 2957, 2930,
1731, 1454, 1331, 1244, 1170, 1043, 817, 697 cmÀ1; ESI HRMS m/z
calcd for C28H39N3O5: 498.2962 [M+H]+; found: 498.2981.
N-Butyl-4-[5-(p-tolylethynyl)-1,3,4-oxadiazol-2-yl]aniline
3aw:
Obtained according to the general procedure from 2-(4-iodophen-
yl)-5-(p-tolylethynyl)-1,3,4-oxadiazole (20.1 mg, 0.052 mmol) and
butylamine (15 mL, 0.15 mmol) at room temperature for 40 h. Upon
completion, the reaction mixture was diluted with 10 mL of a 1m
aqueous solution of sodium hydroxide and extracted twice with
ChemCatChem 2016, 8, 1319 – 1328
1327
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim