JOURNAL OF CHEMICAL RESEARCH 2010 193
m/z Calcd [M+]: 384. Found: 385 [M+1]. HRMS (ESI): m/z Calcd
[M+]: 384.3079. Found: 384.3085 [M +].
N-Pentanoyl-N-{[2p-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-L-
valine (11): To a solution of compound 10 (0.4 g, 0.89 mmol) in meth-
anol (5 mL) was added 1 N NaOH (1 mL) aq. solution and stirred
the reaction mixture at 25 °C for 12 h. The progress of reaction is
monitored by TLC and no starting material was observed. The reac-
tion mixture was diluted with methyl tertiary butyl ether (20 mL) and
water (30 mL). The organic phase was separated and the aqueous
layer was acidified with aqueous HCl solution (2N) until a pH of 3
was reached. Extraction was carried out with methyl tertiary butyl
ether (2x30 mL) followed by drying and evaporating to dryness,
to furnish the desired product as a white solid (0.36 g, 95%). and
Methyl N-{[2p-(4, 4-dimethyl-4, 5-dihydro-1, 3-oxazol-2-yl) biphenyl-
4-yl] methyl}-N-pentanoyl-L-valinate (8): Aryl bromide 5 (2 g,
5.20 mmol), bis (pinacolato) diboron (1.71 g, 6.77 mmol), KOAc
(1.53 g, 15.62 mmol) and PdCl2 (dppf) (0.190 g, 0.260 mmol) were
suspended in dry 1,2-dimethoxyethane (20 mL, degassed by sparging
with N2), and heated to 110 ºC for 18 h. The reaction was monitored
by TLC and no starting material was present. So aryl boronate
synthesis is ready and now to the reaction mixture itself Pd (PPh3)4
(0.3 g, 0.260 mmol) was added followed by 2-brmophenyl oxazoline
7 (1.6 g, 6.23 mmol) and 1M sodium carbonate solution (15.5 mL).
The heating was continued for another 6 h and progress of reaction
was monitored by TLC, and maximum consumption of starting mate-
rial (aryl boronate) was observed. After cooling to 25 °C, the solution
was diluted with ethyl acetate (100 mL) washed with H O (2x50 mL)
and brine (2x30 mL), dried over anhyd. MgSO4 an2d concentrated
under reduced pressure. The residue was chromatographed on silica
gel, and elution with a mixture of heptanes and ethyl acetate (70:30)
1
the anticipated product, Valsartan 11, m.p. 114–118 °C; H NMR
(400 MHz, DMSO-d6): δ 12.6 (brs, 1H), 7.72 (m, 4H), 7.24 (m, 1H),
7.15 (m, 2H), 6.94 (m, 1H), 4.58 (m, 1H), 4.40 (m, 1H), 3.33 (m, 1H),
2.25 (m, 1H), 1.52 (m, 6H), 0.9 (m, 3H), 0.84 (m, 3H), 0.74 (m, 3H);
13C NMR (400 MHz, DMSO-d6): δ 174.0, 172.4, 171.8, 141.7, 138.2,
131.54, 131.1, 131.0, 129.3,128.8, 128.2, 127.4, 126.7, 70.3, 63.4,
49.9, 32.9, 28.05, 27.3, 22.2, 20.6, 14.2; ESIMS: m/z Calcd [M+]:
435. Found: 436 [M+H+]; HRMS (ESI): m/z Calcd [M+]: 435.5187.
Found: 435.5125 [M +].
1
yielded the title compound 8 (6.97 g, 85%) as a colourless oil, H
NMR (400 MHz, DMSO-d6) δ 7.09–7.59 (m, 8H), 4.52–4.74 (m, 2H),
4.18–4.20 (d, 1H) 3.71–3.77 (q, 2H); 3.31–3.36 (d, 3H), 2.25–2.33
(m, 2H), 1.90–2.20 (m, 2H), 1.55–1.6 (m, 1H), 1.40–1.45 (2H, m),
1.00–1.20 (6H, m), 0.88–0.91 (3H, t), 0.76–0.80 (6H, m) 13C NMR
(DMSO-d6) δ 14.14, 18.63, 19.69, 22.20, 27.35, 27.67, 28.12, 32.76,
48.52, 51.81, 62.25, 67.91, 78.91, 126.18, 127.58, 128.17, 128.68,
130.28, 130.47, 130.97, 137.23, 139.59, 141.05, 162.37, 170.96,
173.81; ESIMS: m/z Calcd [M+]: 478. Found: 479 [M+H+]; HRMS
(ESI): m/z Calcd [M+]: 478.2832. Found: 478.2930 [M+].
We are grateful for the support of the Sardar Vallabhbhai
National Institute of Technology, Surat and Indian Association
for the Cultivation of Science, Jadavpur, W.B., India for
analytical support.
Received 1 February 2010; accepted 15 March 2010
Paper 100988 doi: 10.3184/030823410X12698758703526
Published online: 28 April 2010
Methyl-N-[(2p-cyanobiphenyl-4-yl) methyl]-N-pentanoyl-L-valinate
(9): To a solution of compound, methyl N-{[2p-(4, 4-dimethyl-4, 5-
dihydro-1, 3-oxazol-2-yl) biphenyl-4-yl] methyl}-N-pentanoyl-L-
valinate 8 (1 g, 2.09 mmol) in dry pyridine (5 mL), phosphorus
oxychloride (0.64 g, 4.18 mmol) was added dropwise at 0 °C. The
resulting solution was stirred at 85 °C (bath temperature under nitro-
gen for 14 h and, after being cooled to room temperature, was poured
into a cold saturated solution of sodium carbonate (100 mL). After
being cooled to room temperature the mixture was quenched by addi-
tion of water, and the resulting emulsion was extracted with ethyl
acetate. The combined organic phases were washed with water, 10%
aqueous cupric sulfate solution, and brine. The solution then was dried
over anhydrous magnesium sulfate, filtered, concentrated under
vacuum, and purified by column chromatography (SiO2, ethyl acetate/
hexane 3:7), yielding compound methyl-N-[(2p-cyanobiphenyl-4-yl)
methyl]-N-pentanoyl-L-valinate 9 as a yellow oil (0.75 g, 90% yield),
1H NMR (400 MHz,DMSO-d6) δ 7.17–7.86 (m, 8H), 4.53–4.87
(m, 2H), 4.13–4.18 (m, 1H), 3.25–3.33 (d, 3H), 2.24–2.35 (m, 2H),
2.00–2.13 (m, 1H), 1.41–1.53 (2H, m), 1.10–1.31 (2H, m), 0.86–1.08
(3H, m), 0.68–0.79 (6H, m) 13C NMR (DMSO-d6) δ 14.16, 18.45,
19.59, 22.21, 27.56, 32,76, 48.39, 52.07, 62.17, 65.09, 110.46, 119.03,
126.72, 127.54, 128.51, 128.63, 130.66, 134.22, 136.86, 139.19,
144.72, 170.59, 174.13; ESIMS: m/z Calcd [M+]: 406. Found: 407
[M+H+], 429 [M+ +Na]; HRMS (ESI): m/z Calcd [M+]: 406.5173.
Found: 406.5092 [M +].
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