European Journal of Organic Chemistry
10.1002/ejoc.202000695
FULL PAPER
H3/3a/4/5/6/7), 1.86 (1H, m, H3/3a/4/5/6/7), 1.78-1.38 (7H, m,
for
C
6
H
8
N
[M-H] 107.1, found 106. The spectroscopic data was
[
50]
H3/3a/4/5/6/7); GC-MS (m/z) calcd for C
spectroscopic data was compared with previously published data.
Decahydroquinoline hydrochloride 2an·HCl: 1H NMR (500 MHz,
CD OD) 3.75-2.65 (3H, m, H2/8a), 2.23-1.05 (13H, m, H3/4/4a/5/6/7/8).
8
H
15N [M] 125.1, found 125. The
compared with previously published data.
Cyclohexylamine hydrochloride 2bk·HCl: H NMR (500 MHz, CD
3.33-3.16 (1H, m, H1), 2.15-1.64 (5H, m, H2/3/4/5/6), 1.47-1.14 (5H, m,
H2/3/4/5/6); ESI-MS (m/z) calcd for C
The spectroscopic data was compared with previously published data.
N,N-Dimethylcyclohexanamine hydrochloride 2bl·HCl: 1H NMR (500
[
38]
1
3
OD)
14N [M+H]+ 100.1, found 100.1.
3
6
H
[
39]
[50]
The spectroscopic data was compared with previously published data.
1
3,4-Dihydroguinazolin 2ao·HCl: H NMR (400 MHz, CD
3
OD) 8.16 (1H,
br, H2), 7.30 (1H, t, J = 7.6 Hz, H6/7), 7.24 (1H, t, J = 7.6 Hz, H6/7), 7.15
1H, d, J = 7.2 Hz, H5/8), 7.06 (1H, d, J = 7.6 Hz, H5/8), 4.81 (2H, s, H4);
ESI-MS (m/z) calcd for C
[M+H]+ 133.08, found 133.08. The
spectroscopic data was compared with previously published data.
MHz, CD
3
OD) 3.18 (1H, m, H1), 2.83 (6H, s, Me), 2.08 (2H, m, H2/6),
(
1.92 (2H, d, J = 13.2 Hz, H3/5), 1.71 (1H, d, J = 13.2 Hz, H4), 1.54-1.16
(5H, m, H2/3/4/5/6); GC-MS (m/z) calcd for C
8
H
9
N
2
8
H
17N [M] 127.1, found 127.
[
40]
[51]
The spectroscopic data was compared with previously published data.
N-isopropylpiperidine·HCl: A solution of pyridine (20.0 L, 248.3 μmol,
1 eq) in acetone (1.2 mL) with 10% Pd/C (26.4 mg, 24.8 mol, 0.1 eq)
was hydrogenated at balloon pressure. After stirring for 15 h at room
temperature, the reaction mixture was separated by filtration through
Celite pad eluting with MeOH. The filterate was added 1N HCl (273 L,
1.1 eq) and then repeated MeOH evaporation of the mixture afforded N-
1
,4,5,6-Tetrahydropyrimidine 2ap·HCl: 1H NMR (500 MHz, CD
7.97 (1H, m, H2), 3.42 (4H, br, H4/6), 2.02 (2H, m, H5); GC-MS (m/z)
[M] 84.1, found 84. The spectroscopic data was
3
OD)
calcd for C
compared with previously published data.
,4,5,6-Tetrahydropyrimidin-2-amine hydrochloride 2aq·HCl: H NMR
400 MHz, CD OD) 3.33 (4H, m, H4/6), 1.92 (2H, quin, H5); GC-MS
m/z) calcd for C [M] 99.1, found 99. The spectroscopic data was
4 8 2
H N
[
41]
1
1
(
(
3
4
H
9
N
3
isopropylpiperidine hydrochloride (144.0 mol, 58%) as a colorless
[
42]
1
compared with previously published data.
crystal; H NMR (500 MHz, CD
3
OD) 3.47 (1H, m, CH), 3.42 (2H, d, J =
1
Piperazine hydrochloride 2ar: H NMR (500 MHz, CD
3
OD) 3.18-3.07
10.9 Hz, H2/6), 2.99 (2H, t, J = 12.0 Hz, H2/6), 1.98 (2H, d, J = 12.6 Hz,
(
8H, m, H2/3/5/6). The spectroscopic data was compared with previously
H3/5), 1.84 (3H, m, H3/4/5), 1.52 (1H, m, H4), 1.35 (6H, m, Me); GC-MS
[
43]
published data.
4
(m/z) calcd for C
8
H
16N [M-H] 126.1, found 126. The spectroscopic data
1
[52]
-(2-Ethoxycarbonylethyl)piperidine acetate 2as·AcOH: H NMR (500
was compared with previously published data.
MHz, CD
H2/6), 2.92 (2H, m, J = 2.5, 13.0 Hz, H2/6), 2.38 (2H, t, J = 7.5 Hz, H8),
.92 (2H, br, H7), 1.90 (3H, s, Ac), 1.61 (3H, m, H3/4/5), 1.42-1.29 (2H,
m, H3/5), 1.25 (3H, t, J = 7.5 Hz, Et); ESI-HRMS (m/z) calcd for
[M+H]+ 186.1494, found 186.1494. The spectroscopic data
3
OD) 4.12 (2 H, q, J = 7.5 Hz, Et), 3.34 (2H, d, J = 12.1 Hz,
Synthesis of 1:
1
Mizoroki-Heck product 3: S2 (170.6 mg, 0.823 mmol, 1.0 eq), palladium
acetate (2.0 mg, 8.8 mol, 1.1 mol%), and tri-o-tolyl phosphine (4.0 mg,
10 2
C H20NO
13.3 mol, 1.6 mol%) were dissolved in DMF (2.0 mL). The solution was
[
44]
was compared with previously published data.
-Piperidin-2’-ylpropan-1-ol acetate 2at·AcOH: 1H NMR (500 MHz,
added bromo veratrole (236.8 L, 1.65 mmol, 2.0 eq). The solution was
degassed and triethylamine (0.8 mL) was added into the solution before
the temperature was raised up to 100 °C. The reaction solution was
stirred for 5 hours at 100 °C and then cooled down to room temperature.
3
CD
3
OD) 3.59 (2H, m, H1), 3.34 (1H, m, H2’), 3.05 (1H, m, H6’), 2.92
(
C
1H, m, H6’), 2.04-1.48 (13H, m, Ac/H2/3/3’/4’/5’); ESI-MS (m/z) calcd for
18NO [M+H]+ 144.13, found 144.13. The spectroscopic data was
8
H
2
It was diluted with ethyl acetate and washed with H O. The aqueous
[
24]
compared with previously published data.
-Benzylpiperidine hydrochloride 2au·HCl: 1H NMR (400 MHz,
CD OD) 7.41-7.21 (5H, m, Ph), 3.35 (2H, m, H2/6), 3.12-2.93 (2H, m,
H6/7), 2.86 (1H, m, H7), 1.85 (3H, m, H3/4/5), 1.72 (1H, m, H4), 1.50 (2H,
m, H3/5); FAB-MS (m/z) calcd for C12
18N [M+H]+ 176.1439, found
76.1440. The spectroscopic data was compared with previously
layer was extracted with ethyl acetate twice and the combined organic
layer was dried over sodium sulfate before concentration. The mixture
was purified through silica gel column chromatography (40% ethyl
acetate in hexane), giving yellow oil product 3 (179.0 mg, 0.521 mmol,
2
3
H
3%); 1H NMR (400 MHz, CDCl
2H, m, H14), 6.76-6.72 (3H, m, H4/7/9), 4.53-4.51 (1H, t, J = 7.4 Hz, H2),
.15-4.09 (2H, m, Et), 3.83 (6H, s, H10/11), 3.25 (2H, m, H3), 1.15-1.12
6
(
4
3
) 8.79-8.78 (2H, m, H15), 7.69-7.68
1
[
33]
published data.
Diphenylmethane 2ba: 1H NMR (500 MHz, CDCl
7
1
3
) 7.30 (4H, m, Ph),
); GC-MS (m/z) calcd for C13 11 [M-H]
67.1, found 167. The spectroscopic data was compared with previously
3H, m, Et); 13C NMR (100 MHz, CDCl
) 194.5, 168.6, 151.0, 149.0,
48.0, 142.3, 130.3, 121.3,120.9, 112.3, 111.4, 61.9, 56.7, 55.9, 34.2,
4.0; ESI-HRMS (m/z) calcd for C19H21NNaO
(
3
.26 (6H, m, Ph), 4.05 (2H, s, CH
2
H
1
1
3
[M+Na]+ 366.1317, found
5
[
45]
published data.
66.1301.
4
-Methylveratrole 2bb: 1H NMR (500 MHz, CDCl
3
) 6.79-6.75 (1H, m,
Ar), 6.73-6.69 (2H, m, Ar), 3.87 (3H, s, OMe) , 3.85 (3H, s, OMe) , 2.31
3H, s, Me); GC-MS (m/z) calcd for C [M] 152.1, found 152. The
Enol triflate 4: 3 (963.2 mg, 2.81 mmol, 1.0 eq) was added to THF (6.4
mL). The mixture was cooled down in water bath before 60% sodium
hydride in oil (134.6 mg, 3.37 mmol, 1.2 eq) was added. After the solution
was stirred at room temperature for
bis(trifluoromethanesulfonimide) (1.2 g, 3.37 mmol, 1.2 eq) was added.
The reaction solution was stirred at room temperature for 25 hours and
then diluted with CH
was extracted with CH
washed with brine and dried over sodium sulfate before concentrated
using evaporator. Purification of the mixture through silica gel column
chromatography (50% ethyl acetate in hexane) afforded yellow oil 4 (1.13
(
9 12 2
H O
[
46]
spectroscopic data was compared with previously published data.
Benzamide 2be: H NMR (400 MHz, CD
3
hours, N-phenyl-
1
3
OD) 2.22 (1H, tt, J = 3.2, 11.6
Hz, H1), 1.89-1.66 (5H, m, H2/3/4/5/6), 1.52-1.19 (5H, m, H2/3/4/5/6);
GC-MS (m/z) calcd for C 13NO [M] 127.1, found 127. The spectroscopic
data was compared with previously published data.
Methylcyclohexane 2bf: 1H NMR (500 MHz, CDCl
7
H
2
Cl
2
. It was washed with H
2
O and the aqueous layer
[
47]
2
Cl twice. The combined organic layer was
2
3
) 1.51 (5H, m,
H2/4/6), 1.23-0.93 (4H, m, H1/3/4/5), 0.8-0.67 (5H, m, Me/H2/6). The
spectroscopic data was compared with previously published data.[48]
Trifluoromethylcyclohexane 2bg: 1H NMR (500 MHz, CD
(
OD) 2.01
1H, m, H1), 1.89-1.56 (5H, m, H2/3/4/5/6), 1.32-1.09 (5H, m, H2/3/4/5/6).
The spectroscopic data was compared with previously published data.[38]
Cyclohexanol 2bh: 1H NMR (500 MHz, CD
OD) 3.52 (1H, m, H1),
.76-1.06 (10H, m, H2/3/4/5/6); GC-MS (m/z) calcd for C 12O [M] 100.1,
3
1
g, 2.38 mmol, 85%); H NMR (500 MHz, CDCl
3
) 8.72-8.69 (2H, m, H15),
7
.34-7.33 (2H, m, H14), 6.83-6.70 (3H, m, H4/7/9), 3.92-3.86 (10H, m,
Et/H3/10/11), 0.87-0.84 (3H, t, J = 7.5 Hz, Et); 13C NMR (125 MHz,
3
CDCl ) 165.4, 150.9, 150.3, 149.1, 148.3, 146.6, 140.0, 131.7, 127.9,
22.9, 121.1, 116.9, 112.2, 111.4, 62.0, 56.0, 34.6, 13.5; ESI-HRMS
3
1
6
H
1
found 100. The spectroscopic data was compared with previously
published data.[48]
Dimethyl-1,2-cyclohexanedicarboxylate 2bi: 1H NMR (500 MHz,
+
(
m/z) calcd for C20
N-Benzyl piperidine 5: S4 (744.9 mg, 2.22 mmol, 1.0 eq) was added to
CH Cl (3.4 mL). Benzyl bromide (0. 4 mL, 3.40 mmol, 1.5 eq) was
21 3 7
H F NO S [M+H] 476.0990, found 476.1019.
2
2
CDCl
2H, m, H3/6), 1.41 (2H, m, H4/5), 0.92 (2H, m, H4/5); GC-MS (m/z)
calcd for C10 [M] 200.1, found 200. The spectroscopic data was
compared with previously published data.
Benzylamine acetate 2bj·AcOH: 1H NMR (500 MHz, CD
.32 (5H, m, Ph), 4.09 (2H, s, CH ), 1.89 (3H, s, Ac); GC-MS (m/z) calcd
3
) 3.68 (6H, s, OMe), 2.83 (2H, m, H1/2), 2.00 (2H, m, H3/6), 1.78
added to the mixture before the solution was cooled down to 0 °C. After
triethylamine (0.95 mL, 6.79 mmol, 3.0 eq) was added, the reaction
solution was stirred at room temperature for 40 hours. Concentration and
purification of the mixture through silica gel column chromatography
(
16 4
H O
[
49]
3
OD) 7.53-
(
67% ethyl acetate in hexane) afforded colorless oil 5 (563.6 mg, 1.32
7
2
1
mmol, 60%); H NMR (500 MHz, CDCl
3
) 7.31-7.22 (5H, m, H18/19/20),
1
0
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