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equivalents of 1 M NaOH was added to the solution. The reac- (125 MHz, CDCl
tion mixture was reuxed for 2 h, the solvent removed under 128.78, 128.25, 127.70, 126.02, 111.60, 111.09, 70.62, 63.57. UV-
3
): d ¼ 162.22, 156.54, 140.81, 136.61, 133.70,
ꢂ1
ꢂ1
vacuum, quenched with water and neutralised by addition of vis (lmax/nm (3/M cm ), DMSO): 330 (13 828), 284 (19 078).
M HCl until the pH reached 1. A white solid precipitated. The
1
crude product was ltered, washed with water and the solvent
removed under vacuum. The creamy yellow precipitate as
a crude product was used for the further reaction without
Pentahydroxypentamer, 2
Boron tribromide (0.008 mL, 0.078 mmol) was added to a solu-
+
tion of pentabenzyloxypentamer, 1 (10 mg, 0.008 mmol) in dry
purication. Yield: 0.069 g, 99%. HRMS (ESI) [M + Na] ¼ calcd
ꢀ
1
CH
2
Cl
2
(20.0 mL) at 0 C. The mixture was stirred at r.t. over-
3
26.0621 m/z, found 326.0626 m/z. H NMR (300 MHz, CDCl
3
):
night under N
2
atmosphere. The solution was decanted off. The
d ¼ 7.88 (d, 1H, J ¼ 3.2 Hz), 7.64 (d, 1H, J ¼ 3.2 Hz), 7.43–7.35
1
3
remaining solid was washed with water, the solvent removed
under vacuum, re-dissolved in MeOH (20 mL) and a small
portion of the crude product was puried by analytical RP-HPLC
(
1
1
m, 5H), 5.13 (s, 2H), 4.02 (s, 3H). C NMR (75 MHz, CDCl ): d ¼
3
66.45, 154.40, 147.19, 145.16, 135.25, 129.00, 128.79, 127.75,
26.07, 122.76, 116.71, 71.33, 64.94.
(eluted with 100% water for 5 min and 0–100% linear increase
ꢂ1
of MeOH for 25 min at a maintained ow rate of 1 mL min ) to
give a white solid. Yield: 1.9 mg, 29%. HRMS (ESI) [M + Na] ¼
calcd 848.2027 m/z, found 848.2013 m/z.
3-Amino-5-hydroxy-2-methoxybenzoic acid, 11
35
+
A mixture of 5-(benzyloxy)-2-methoxy-3-nitrobenzoic acid, 10
0.60 g, 2.0 mmol) and Pd/C (0.06 g, 10% in mass) in MeOH (30
(
mL) was added into a hydrogenation vessel and the nitro group
was reduced at 40 C and 450 kPa for 18 h. Filtration and
ꢀ
Fluoropentamer, 3
3
removal of the solvent gave a brown sticky oil product. Yield: POCl (0.21 mL, 2.2 mmol) was added to a solution of 3-amino-
+
0
2
9
.348 g, 96%. HRMS (ESI) [M + Na] ¼ calcd 206.0429 m/z, found 2-uorobenzoic acid, 14 (0.17 g, 1.1 mmol) in dry MeCN (10 mL)
1
06.0428 m/z. H NMR (500 MHz, DMSO-d ): d ¼ 12.07 (s, 1H), at r.t. The mixture was stirred vigorously for 10 min. Et
N (0.44
3
6
.00 (s, 1H), 6.28 (d, 1H, J ¼ 2.9 Hz), 6.23 (d, 1H, J ¼ 2.9 Hz), 4.97 mL, 3.3 mmol) was added to the reaction mixture which was
1
3
(
s, 2H), 3.59 (s, 3H). C NMR (128 MHz, DMSO-d
6
): d ¼ 167.64, stirred overnight at r.t. Aer removal of the solvent, the residue
Cl
(50 mL ꢁ 2), MeOH (50 mL) and DMF
(20 mL) to give an off-white solid. Yield: 7.0 mg, 4.0%. HRMS
1
l
53.15, 142.99, 138.47, 125.81, 104.83, 103.48, 60.07. UV-vis was washed with CH
max/nm (3/M cm ), DMSO): 330 (4112), 267 (3912).
2
2
ꢂ1
ꢂ1
(
+
1
(
ESI) [M + Na] ¼ calcd 708.1282 m/z, found 708.1303 m/z. H
3
-Amino-5-(benzyloxy)-2-methoxybenzoic acid, 12
NMR (400 MHz, DMSO-d
6
): d ¼ 10.21 (s, 5H), 8.40 (t, 5H, J ¼ 1.5
Hz), 7.65 (t, 5H, J ¼ 1.5 Hz), 7.44 (t, 5H, J ¼ 7.8 Hz).
A mixture of 5-(benzyloxy)-2-methoxy-3-nitrobenzoic acid, 10
0.70 g, 2.3 mmol) and Pt/C (0.07 g, 10% in mass) in MeOH (80
(
mL) was added into a hydrogenation vessel and the nitro group
was reduced at 40 C and 450 kPa for 18 h. Filtration and
Conflicts of interest
ꢀ
There are no conicts to declare.
removal of the solvent gave a red/brown sticky oil product.
+
Yield: 0.608 g, 97%. HRMS (ESI) [M + H] ¼ calcd 274.1079 m/z,
+
found 274.1068 m/z, [M + Na] ¼ calcd 296.0899 m/z, found
Acknowledgements
1
2
7
(
96.0885 m/z. H NMR (300 MHz, CDCl
3
): d ¼ 7.40–7.37 (m, 5H),
.08 (d, 1H, J ¼ 2.8 Hz), 6.06 (d, 1H, J ¼ 2.8 Hz), 5.02 (s, 2H), 3.88 SJN is grateful to the University of Auckland, Faculty of Science
1
3
s, 3H). C NMR (75 MHz, CDCl
3
): d ¼ 166.44, 156.02, 141.28, for the award of a PhD fellowship.
41.14, 136.67, 128.74, 128.22, 127.66, 122.52, 108.89, 105.94,
1
7
3
ꢂ1
ꢂ1
0.49, 61.45. UV-vis (lmax/nm (3/M cm ), DMSO): 461 (477),
28 (3141), 264 (3321).
Notes and references
1
P. Siemsen, R. C. Livingston and F. Diederich, Angew. Chem.,
Int. Ed., 2000, 39, 2632–2657.
Pentabenzyloxypentamer, 1
POCl (0.34 mL, 3.7 mmol) was added to a solution of 3-amino-
-(benzyloxy)-2-methoxybenzoic acid, 11 (0.50 g, 1.8 mmol) in
dry MeCN (20 mL) at r.t. The mixture was stirred vigorously for
0 min. Et N (0.75 mL, 5.4 mmol) was added to the reaction
mixture which was stirred overnight at r.t. Aer removal of the
solvent, the residue was puried by ash column chromatog-
2 2
raphy on silica eluted with EtOAc : CH Cl (1 : 25). The rst and
3
2 P. A. Vigato, S. Tamburini and L. Bertolo, Coord. Chem. Rev.,
2007, 251, 1311–1492.
3 M. Fujita, Chem. Soc. Rev., 1998, 27, 417–425.
4 C. O. Kappe and E. Van der Eycken, Chem. Soc. Rev., 2010, 39,
1280–1290.
5 A. Deiters and S. F. Martin, Chem. Rev., 2004, 104, 2199–2238.
6 K. S. Mali, N. Pearce, S. De Feyter and N. R. Champness,
Chem. Soc. Rev., 2017, 46, 2520–2542.
7 D. Bonifazi, S. Mohnani and A. Llanes-Pallas, Chem.–Eur. J.,
2009, 15, 7004–7025.
5
1
3
third yellow fractions were impurities and the second fraction
was the product as a white solid. Yield: 65 mg, 14%. HRMS (ESI)
+
1
[
(
(
M + Na] ¼ calcd 1298.4375 m/z, found 1298.4362 m/z. H NMR
500 MHz, CDCl ): d ¼ 10.93 (s, 5H), 8.72 (d, 5H, J ¼ 3.2 Hz), 7.59
8 O. Guillermet, E. Niemi, S. Nagarajan, X. Bouju, D. Martrou,
A. Gourdon and S. Gauthier, Angew. Chem., Int. Ed., 2009, 48,
1970–1973.
3
d, 5H, J ¼ 3.2 Hz), 7.51 (d, 10H, J ¼ 7.4 Hz), 7.43 (t, 10H, J ¼ 7.7
1
3
Hz), 7.36 (d, 5H, J ¼ 7.2 Hz), 5.20 (s, 30H), 4.01 (s, 15H). C NMR
8392 | RSC Adv., 2019, 9, 8389–8393
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