10.1002/ejoc.201800048
European Journal of Organic Chemistry
FULL PAPER
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tert-butyl 2-bromopentanedioate, or 1-tert-butyl 5-methyl 2-
bromopentanedioate (2.5 mmol) was added dropwise. Once the
addition was complete, the ice bath was removed and the
reaction was kept at room temperature for 3 h. The solvent was
then removed, washed with water (20 mL), and extracted with
dichloromethane. Evaporation of dichloromethane under
vacuum gave the crude product. The crude product was further
purified by FC (dichloromethane/methanol/NH4OH, 90/9/1, V/V/V)
to yield the desired product.
CD3OD, 25 C) δ: 7.46-7.29 (m, 5H), 3.84 (d, J = 4.64 Hz, 3H),
3.72 (s, 3H), 3.37-3.31 (m, 1H), 3.18-2.72 (m, 12H), 2.50 (t, J =
7.36 Hz, 2H), 2.10-2.05 (m, 1H), 1.94-1.87 (m, 1H), 1.52 (s, 9H).
13C NMR (100 MHz, CD3OD, 25 C) δ: 173.64, 172.05, 138.07,
129.29, 128.38, 127.42, 81.79, 63.77, 60.56, 56.94, 33.12, 43.46,
30.73, 27.15, 24.84. HRMS calcd for C23H37N3O4: 419.2784,
found: 420.2905 [M + H]+.
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1-Tert-butyl 5-methyl 2-(4-benzyl-7-(2-tert- butoxy-2-
oxoethyl)-1,4,7-triazonan-1-yl) pentanedioate (6): To
a
4a: Following the general procedure, treatment of 3a (50 mg,
0.15 mmol) with N,N-diisopropylethylamine (77 mg, 0.6 mmol)
and tert-butyl bromoacetate (74 mg, 0.38 mmol) yielded 4a (67
mg, 79.2%) as a colorless oil. 1H NMR (400 MHz, CDCl3, 25 oC)
δ: 3.69 (s, 3H), 3.33 (s, 4H), 3.20-3.16 (m, 1H), 2.95-2.78 (m,
12H), 2.57-2.47 (m, 2H), 2.01-1.83 (m, 2H), 1.46 (s, 27H). 13C
NMR (100 MHz, CDCl3, 25 oC) δ: 173.97, 172.56, 171.67, 80.60,
66.89, 60.36, 59.33, 56.17, 55.57, 53.23, 51.49, 30.83, 28.30,
28.23, 25.31, 21.02, 14.19. HRMS calcd for C28H51N3O8:
557.3676, found: 558.3807 [M + H]+.
solution of (100 mg, 0.24 mmol) and N,N-
5
diisopropylethylamine (47 mg, 0.36 mmol) in acetonitrile (20 mL)
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at 0 C, tert-butyl bromoacetate (70 mg, 0.36 mmol) was added
dropwise. Once the addition was completed, the ice bath was
removed and the reaction was kept at room temperature for 3 h.
The solvent then was removed, washed with water (20 mL), and
extracted with dichloromethane. dichloromethane was removed
under vacuum to give a crude product, which was further
purified by FC (dichloromethane/methanol/NH4OH, 90/9/1, V/V/V)
to yield 6 (105 mg, 83.1%) as a colorless oil. 1H NMR (400 MHz,
CDCl3, 25 oC) δ: 7.64-7.62 (m, 2H), 7.41-7.39 (m, 3H), 3.68-3.64
(m, 5H), 4.57-4.54(m, 1H), 3.66-3.61(m, 5H), 2.74-2.64 (m, 14H),
2.33-2.30 (m, 2H), 2.00-1.95 (m, 1H), 1.90-1.78 (m, 1H), 1.48 (s,
9H), 1.39 (s, 9H). 13C NMR (100 MHz, CDCl3, 25 oC) δ: 173.29,
171.29, 130.92, 130.50, 130.04, 129.36, 82.34, 64.73, 59.85,
52.21, 51.75, 50.23, 30.90, 28.08, 28.01. HRMS calcd for
C29H47N3O6: 533.3465, found: 534.3627 [M + H]+.
4b: Following the general procedure, treatment of 3b (50 mg,
0.20 mmol) with N,N-diisopropylethylamine (106 mg, 0.82 mmol)
and 5-benzyl 1-tert-butyl 2-bromopentanedioate (183 mg, 0.51
1
mmol) yielded 4b (123 mg, 75.2%) as a colorless oil. H NMR
(400 MHz, CDCl3, 25 oC) δ: 7.37 (s, 10H), 5.13 (s, 4H), 3.26-3.17
(m, 4H), 2.93-2.80 (m, 10H), 2.65-2.62 (m, 2H), 2.55-2.49 (m,
4H), 2.09-1.89 (m, 4H), 1.46-1.44 (m, 27H). 13C NMR (100 MHz,
CDCl3, 25 oC) δ: 173.17, 172.40, 171.69, 136.06, 128.54, 128.22,
85.90, 80.83, 67.18, 66.21, 55.92, 54.08, 53.68, 31.23, 28.28,
25.35. HRMS calcd for C44H65N3O10: 795.4670, found:
796.4801 [M + H]+.
1-Tert-butyl 5-methyl 2-(4-(2-tert-butoxy-2- oxoethyl)-1,4,7-
triazonan-1-yl) pentanedioate(7): To a solution of 6 (100 mg,
0.19 mmol) in methanol (10 mL), 10% Pd/C (10 mg) was added.
The mixture was stirred at room temperature under 1 atm H2 for
4 h. The catalyst was then removed by filtration, and the filtrate
evaporated under vacuum to yield 7 (83 mg, 100 %) as a
colorless oil, without further purification. 1H NMR (400 MHz,
4c: Following the general procedure, treatment of 3c (100 mg,
0.36 mmol) with N,N-diisopropylethylamine (106 mg, 0.82 mmol)
and 1-tert-butyl 5-methyl 2-bromopentanedioate (238 mg, 0.82
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CD3OD, 25 C) δ: 3.70 (s, 3H), 3.50 (s, 2H), 3.44-3.41 (m, 1H),
1
3.28-2.79 (m, 12H), 2.48 (t, J = 7.2 Hz, 2H), 2.11-2.03 (s, 1H),
mmol) yielded 4c (175 mg, 71.6%) as a colorless oil. H NMR
1.99-1.90 (m, 1H), 1.51-1.48 (m, 18H). 13C NMR (100 MHz,
(400 MHz, CDCl3, 25 oC) δ: 4.16-4.08 (m, 4H), 3.67 (s, 6H),
3.16-3.06 (m, 4 H), 2.99-2.83 (m, 10H), 2.48-2.38 (m, 4H), 2.04-
1.95 (m, 2H), 1.89-1.82 (m, 2H), 1.44 (s, 18H), 1.32 (t, J = 7.02
Hz, 12H). 13C NMR (100 MHz, CDCl3, 25 oC) δ: 173.67, 172.27,
80.89, 67.32, 61.64, 61.60, 61.58, 61.53, 56.69, 56.62, 53.93,
53.70, 53.63, 51.50, 31.06, 28.27, 25.47, 16.56, 16.51. HRMS
calcd for C31H58N3O11P: 679.3809, found: 680.3977 [M + H]+.
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CD3OD, 25 C) δ: 173.85, 171.85, 171.64, 81.60, 63.90, 56.36,
54.53, 50.90, 44.53, 44.06, 43.43, 42.57, 30.29, 27.15, 27.06,
24.70. HRMS calcd for C22H41N3O6: 443.2995 found:
444.3168 [M + H]+.
General synthetic procedures for 8a-c: To a solution of 7 (1
mmol) and N,N-diisopropylethylamine (2 mmol) in acetonitrile
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(20 mL) at 0 C, 5-benzyl 1-tert-butyl 2-bromopentanedioate or
4d: Following the general for synthesis phosphate, treatment of
3a (100 mg, 0.30 mmol), with paraform (22 mg, 0.75 mmol),
diethyl phosphite (104 mg, 0.75 mmol), and p-toluenesulfonic
acid (6 mg, 0.03 mmol) yielded 4d (144 mg, 75.4%) as a
methyl bromoacetate (1.2 mmol) was added dropwise. Once the
addition was complete, the ice bath was removed and the
reaction was kept at room temperature for 3 h. The solvent was
then removed, washed with water (20 mL), and extracted by
dichloromethane. Vacuum removal of dichloromethane gave the
crude product, which was further purified by FC
(dichloromethane/ methanol/NH4OH, 90/9/1, V/V/V) to yield the
desired product.
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colorless oil. H NMR (400 MHz, CDCl3, 25 oC) δ: 4.15-4.08 (m,
8H), 3.66 (s, 3H), 3.20-2.79 (m, 16H), 2.48-2.42 (m, 2H), 2.02-
1.95 (m, 1H), 1.88 (br s, 1H), 1.43 (s, 9H), 1.31 (t, J = 7.02 Hz,
12H). 13C NMR (100 MHz, CDCl3, 25 oC) δ: 173. 64, 173.29,
81.05, 67.14, 61.72, 56.84, 56.19, 53.89, 53.02, 52.33, 51.52,
30.93, 28.20, 25.30, 20.96, 16.53, 16.48. HRMS calcd for
C26H53N3O10P2: 629.3206, found: 630.3286 [M + H]+.
8a: Following the general procedure, treatment of 7 (50 mg,
0.11 mmol) with N,N-diisopropylethylamine (29 mg, 0.22 mmol)
and 5-benzyl 1-tert-butyl 2-bromopentanedioate (48 mg, 0.14
mmol) afforded 8a (64 mg, 78.3%) as a colorless oil. H NMR
(400 MHz, CDCl3, 25 C) δ: 7.37 (s, 5H), 5.14 (s, 2H), 3.68 (s,
3H), 3.27 (d, J = 5.6 Hz, 5H), 3.16-3.14 (m, 2H), 2.95-2.89 (m,
4H), 2.82-2.80 (m, 6H), 2.64 (d, J = 8.5 Hz, 5H), 2.56-2.44 (m,
4H), 2.06-1.94 (m, 2H), 1.92-1.84 (m, 2H), 1.46 (s, 27H). 13C
NMR (100 MHz, CDCl3, 25 oC) δ: 173.57, 172.98, 171.93,
1-Tert-butyl
5-methyl
2-(4-benzyl-1,4,7-triazonan
-1-
1
yl)pentanedioate(5): To a solution of 2a (200 mg, 0.39 mmol) in
ethanol (15 mL), 10% Pd/C (20 mg) was added. The mixture
was stirred at room temperature under 1 atm H2 for 12 h. The
catalyst was then removed by filtration, and the filtrate
evaporated under vacuum to yield 5 (164 mg, 100%) as
colorless oil, without further purification. 1H NMR (400 MHz,
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