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Organic & Biomolecular Chemistry
Page 6 of 9
DOI: 10.1039/C8OB01330F
ARTICLE
Journal Name
anhydrous THF was injected via the septum followed by 1,2-
dibromoethane (10 µL, 0.1 mmol). The mixture was heated in a
microwave oven at 85°C for 5 minutes. TMSCl (2.5 µL, 0.02
mmol) was added to the suspension and once again it was
heated at 85°C for 5 minutes. 4-Bromobenzyl bromide (500 mg,
2 mmol) was then added as a solution in 2 mL THF and the vial
was heated for 1h at 70°C. Iodometric titration indicated that
the obtained solution of 4-bromobenzyl zinc bromide had a
concentration of 0.4 M.
HMMS(ESI): [M+H]+ (C32H32N2O6Br+) m/z Calcd: 619.1443, m/z
found: 619.1436
1-(4'-(Dimethylamino)-4-nitro-[1,1'-biphenyl]-3-yl)-2-(4'-
methoxy-[1,1'-biphenyl]-4-yl)ethyl
acetate (7b):
2-(3,4-dimethoxyphenyl)
In a microwave vial, 52 mg of 6 (0.084 mmol) with 15 mg of 4-
methoxyphenyl boronic acid (0.1 mmol) and potassium
carbonate (30 mg, 0.21 mmol) were dissolved in 2 mL of
ethanol, 1 mL of water and 7 mL of toluene (2/1/7 in vol.). The
2-(4-Bromophenyl)-1-(4'-(dimethylamino)-4-nitro-[1,1'-
biphenyl]-3-yl)ethan-1-ol (5):
mixture was degassed
Pd(PPh3)4 (5 mg, 4.2x10-3 mmol) was added and the mixture was
degassed more time before heating under microwave
2 times (freeze-thaw cycles) then
In 10 mL of anhydrous THF, 4 (130 mg, 0.48 mmol) was
dissolved. At -78°C, the solution of 4-bromobenzyl zinc bromide
(3.6 mL, 1.44 mmol) was added dropwise and the mixture was
stirred for 1h at -78°C and left to warm up to room temperature
and stirred overnight. The reaction was quenched with 10% HCl
and extracted with water and ethyl acetate and the crude
compound was purified on column with heptane/AcOEt 85/15 in
vol. as eluent to afford 5 as orange-red paste (210 mg, 80 %, Rf =
0.32 AcOEt/heptane 15/85 in vol.).
1
radiations at 80°C for 45 minutes. The solvents were
evaporated, and the residue was extracted with ethyl acetate,
washed with water and dried over MgSO4. The solvent was
evaporated under vacuum and the crude product was purified
over column with silica gel using 40/60 AcOEt/heptane as eluent
to afford product 7b as reddish paste (25 mg, 46 %, Rf = 0.32
AcOEt/heptane 40/60 in vol.).
The same procedure was followed for the synthesis of 7a (4-
(dimethyl amino) phenyl boronic acid) yield 55% and 7c (4-
nitrophenyl boronic acid) yield 58%.
3
1H NMR (400 MHz, CDCl3): δ = 8.08 (d, J(H,H) = 8 Hz, 1H), 8.01
(s, 1H), 7.59 (d, 3J(H,H) = 9.6 Hz, 4J(H,H) = 2.2 Hz, 1H), 7.55 (d,
3J(H,H) = 9.6 Hz, 2H), 7.48 (d, 3J(H,H) = 9.6 Hz, 2H), 7.23 (d,
3J(H,H) = 9.6 Hz, 2H), 6.79 (d, 3J(H,H) = 9.6 Hz, 2H), 5.59 (d,
1H NMR (400 MHz, CDCl3): δ = 8.08 (d, 3J(H,H) = 8.4 Hz, 1H), 7.54
3
3
(d, J(H,H) = 8.8 Hz, 2H), 7.52 (d, J(H,H) = 7.6 Hz, 1H), 7.45 (d,
3J(H,H) = 8.4 Hz, 2H), 7.31 (s, 1H), 7.19-7.24 (m, 4H), 6.98 (d,
3J(H,H) = 9.8 Hz, 2H), 6.67-6.72 (m, 5H), 6.63 (d, 3J(H,H) = 8.4 Hz,
1H), 3.86 (s, 3H), 3.77 (s, 3H), 3.70 (s, 3H), 3.52 (s, 2H), 3.39 (d,
3J(H,H) = 14 Hz, 1H), 3.05-3.11 (dd, 2J(H,H) = 22.8 Hz, 3J(H,H) =
15.2 Hz, 1H), 3.02 (s, 6H) ppm.
3
3J(H,H) = 10 Hz, 1H), 3.26 (d, J(H,H) = 12.4 Hz, 1H), 3.03 (s, 6H),
2.8-2.86 (dd, 2J(H,H) = 23, 3J(H,H)= 13.6, 1H) ppm.
+
HRMS(ESI): [M+H]+ (C22H22N2O3 ) m/z Calcd: 441.0703, m/z
found: 441.0177.
+
2-(4-Bromophenyl)-1-(4'-(dimethylamino)-4-nitro-[1,1'-
biphenyl]-3-yl)ethyl-2-(3,4-dimethoxyphenyl)acetate (6):
In 25 mL anhydrous dichloromethane, compound 5 (450 mg,
1.02 mmol) was dissolved and 2-(3,4-dimethoxyphenyl) acetic
acid (300 mg, 1.53 mmol) was added along with 4-dimethyl
aminopyridine DMAP (7 mg, 0.051 mmol) under argon. At 0°C,
N, N’-diisopropyl carbodiimide DIC (0.24 mL, 1.53 mmol) was
added dropwise and the reaction was stirred for 1h at 0°C, then
for 2h at room temperature. The reaction was monitored by
HPLC. The mixture was filtered on a glass-frit funnel and the
filtrate was extracted with dichloromethane and water. To
remove diisopropyl urea salts, the product is dissolved in cold
acetonitrile. The crude product was purified over column with
silica gel using 20/80 AcOEt/heptane in vol. as eluent to afford 6
as orange powder. (430 mg, 68 %, Rf = 0.38 AcOEt/heptane
20/80 in vol.)
HRMS(ESI): [M+H]+ (C39H39N2O7 ) m/z Calcd: 647.2757, m/z
found: 647.2767.
1-(4'-(Dimethylamino)-4-nitro-[1,1'-biphenyl]-3-yl)-2-(4'-
(dimethylamino)-[1,1'-biphenyl]-4-yl)ethyl
dimethoxyphenyl)acetate (7a):
2-(3,4
This compound was obtained in 55% yield.
1H NMR (400 MHz, CDCl3): δ = 8.08 (d, 3J(H,H)= 9.36 Hz, 1H),
7.52 (d, 3J(H,H) = 9.6 Hz, 4J(H,H) = 2.2 Hz, 1H), 7.46 (d, 3J(H,H) =
7.6 Hz, 2H), 7.31 (s, 1H), 7.19-7.22 (m, 4H), 6.82 (d, 3J(H,H) = 7.6
3
Hz, 2H), 6.68-6.71 (m, 5H), 6.63 (d, J(H,H) = 8.8 Hz, 1H), 3.77 (s,
3H), 3.71 (s, 3H), 3.53 (s, 2H), 3.38 (d, 3J(H,H) = 14.4 Hz, 1H),
3.05-3.11 (dd, 2J(H,H) = 23.6 Hz, 3J(H,H) = 13.6 Hz, 1H), 3.01 (s,
6H), 3.00 (s, 6H) ppm.
HRMS(ESI): [M+H]+ (C40H42N3O6 ) m/z Calcd: 660.3073, m/z
+
found: 660.3047.
1H NMR (400 MHz, CDCl3): δ = 8.1 (d, 3J(H,H) = 8 Hz, 1H), 7.55
3
3
(d, J(H,H) = 9.6 Hz, 4J(H,H) = 2.2 Hz, 1H), 7.41 (d, J(H,H) = 9.6
Hz, 2H), 7.38 (s, 1H), 7.23 (d, 3J(H,H) = 9.6 Hz, 2H), 7.18 (d, 3J(H,H)
= 9.6 Hz, 2H), 6.79 (d, 3J(H,H) = 9.6 Hz, 2H), 6.65-6.75 (m, 3H),
6.57 (d, 3J(H,H) = 10 Hz, 1H), 3.85 (s, 3H), 3.75 (s, 3H), 3.52 (s,
2H), 3.32 (d, 3J(H,H) = 12.4 Hz, 1H), 3.16 (s, 6H), 2.9-3.01 (dd,
2J(H,H) = 23 Hz, 3J(H,H) = 13.6 Hz, 1H) ppm.
1-(4'-(Dimethylamino)-4-nitro-[1,1'-biphenyl]-3-yl)-2-(4'-nitro-
[1,1'-biphenyl]-4-yl)ethyl 2-(3,4-dimethoxyphenyl)acetate (7c):
This compound was obtained in 58% yield.
1H NMR (400 MHz, CDCl3): δ = 8.17 (d, 3J(H,H) = 8.8 Hz, 2H), 7.96
3
3
4
(d, J(H,H) = 9.6 Hz, 1H), 7.6 (d, J(H,H) = 7.6 Hz, J(H,H) = 2.2
3
3
Hz, 2H), 7.41 (d, J(H,H) = 8.8 Hz, 1H), 7.38 (d, J(H,H) = 8.8 Hz,
2H), 7.18 (d, 3J(H,H) = 8 Hz, 2H), 7.13 (s, 1H), 7.09 (d, 3J(H,H) = 6.8
6 | J. Name., 2012, 00, 1-3
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