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K. Tangdenpaisal et al. / Tetrahedron 65 (2009) 4316–4325
4.4.5. Methyl 4-benzyloxy-2-(4-methoxy)benzyloxybenzoate (4e)
Mp (MeOH) 71–73 ꢀC. IR (neat): nmax 2949, 1721, 1606, 1514,
56.2, 70.4, 94.1, 102.0, 107.5, 113.6, 126.8, 127.7, 128.4, 133.7, 136.5,
160.0, 161.6, 166.1. LRMS (EI) m/z (rel intensity) 302 (Mþ, 15), 270
(54), 238 (32), 91 (100), 65 (13). TOF-HRMS calcd for C17H19O5
(MþHþ) 303.1227, found 303.1228.
1244, 1174, 1027 cmꢁ1 1H NMR (200 MHz, CDCl3):
. d 3.82 (s, 3H),
3.87 (s, 3H), 5.07 (s, 4H), 6.57–6.63 (m, 2H), 6.93 (d, J¼8.8 Hz, 2H),
7.37–7.45 (m, 6H), 7.88 (d, J¼8.8 Hz, 2H). 13C NMR (50 MHz, CDCl3):
d
51.6, 55.2, 70.1, 70.3, 101.4, 105.9, 113.0, 113.9, 127.5, 128.2, 128.4,
4.4.12. Methyl 2-(4-methoxy)benzyloxy-4-methoxymethyloxy-
benzoate (4l)
128.5, 128.7, 133.8, 136.1, 159.1, 160.2, 163.1, 166.1. LRMS (EI) m/z (rel
intensity) 378 (Mþ, 11), 287 (15), 121 (100), 91 (28). TOF-HRMS
calcd for C23H23O5 (MþHþ) 379.1540, found 379.1542.
IR (neat): nmax 2951, 1722, 1606, 1577, 1514, 1244 cmꢁ1. 1H NMR
(200 MHz, CDCl3):
d 3.47 (s, 3H), 3.81 (s, 3H), 3.86 (s, 3H), 5.10 (s,
2H), 5.18 (s, 2H), 6.60–6.73 (m, 2H), 6.92 (d, J¼8.8 Hz, 2H), 7.43 (d,
4.4.6. Methyl 4-benzyloxy-2-methoxymethyloxybenzoate (4f)
Mp (MeOH) 61–62 ꢀC. IR (neat): nmax 2951, 1724, 1607, 1255,
J¼8.8 Hz, 2H), 7.84 (d, J¼8.8 Hz, 1H). 13C NMR (50 MHz, CDCl3):
d
51.7, 55.3, 56.2, 70.5, 94.3, 102.4, 107.7, 114.0, 128.6, 128.7, 133.6,
1142 cmꢁ1. 1H NMR (200 MHz, CDCl3):
d
3.52 (s, 3H), 3.86 (s, 3H),
159.3, 160.2, 161.7, 166.2. LRMS (EI) m/z (rel intensity) 332 (Mþ, 2),
122 (9), 121 (100), 91 (5), 77 (4). TOF-HRMS calcd for C18H21O6
(MþHþ) 333.1333, found 333.1333.
5.09 (s, 2H), 5.24 (s, 2H), 6.64 (dd, J¼8.8, 2.2 Hz, 1H), 6.83 (d,
J¼2.2 Hz, 1H), 7.38–7.48 (m, 5H), 7.83 (d, J¼8.8 Hz, 1H). 13C NMR
(50 MHz, CDCl3):
d 51.7, 56.3, 70.9, 95.1, 103.4, 107.5, 113.4, 127.5,
128.2, 128.6, 133.4, 136.1, 158.9, 162.9, 165.9. LRMS (EI) m/z (rel in-
tensity) 302 (Mþ, 9), 238 (27), 91 (100). TOF-HRMS calcd for
C17H19O5 (MþHþ) 303.1227, found 303.1222.
4.5. General procedure for the deprotection
To a stirred solution of 3a–d or 4a–l (1.0 equiv) in toluene
(20 mL/mmol of 3a–d or 4a–l) was added the solid-supported acid
(either Amberlyst-15 (loading: 4.81 mmol/g) or PTS-Si (loading:
0.81 mmol/g); 0.6 equiv). The reaction mixture was kept at tem-
perature and for the duration as indicated in Table 2. The reaction
mixture was filtered and the solid-supported material was washed
extensively with EtOAc. The filtrate was then concentrated under
reduced pressure. The product was obtained by following column
chromatography on silica (20% EtOAc/hexanes).
4.4.7. Methyl 2-isopropoxy-4-(4-methoxy)benzyloxybenzoate (4g)
IR (neat): nmax 2978, 1724, 1604, 1514, 1243, 1109 cmꢁ1. 1H NMR
(200 MHz, CDCl3):
d
1.36 (d, J¼6.0 Hz, 6H), 3.81 (s, 3H), 3.84 (s, 3H),
4.52 (sept, J¼6.0 Hz, 1H), 4.99 (s, 2H), 6.44–6.62 (m, 2H), 6.92 (d,
J¼8.8 Hz, 2H), 7.35 (d, J¼8.8 Hz, 2H), 7.82 (d, J¼9.6 Hz, 1H). 13C NMR
(50 MHz, CDCl3):
d 21.9, 51.5, 55.2, 69.9, 71.7, 102.7, 105.7, 113.7,
114.0,128.1,129.3, 133.6,159.5,159.7,163.0,166.3. LRMS (EI) m/z (rel
intensity) 330 (Mþ, 2), 121 (100). TOF-HRMS calcd for C19H23O5
(MþHþ) 331.1540, found 331.1536.
4.5.1. Methyl 4-hydroxy-2-isopropoxybenzoate (5a)
Mp (MeOH) 113–115 ꢀC. IR (neat): nmax 3323 (br), 2980, 1698,
4.4.8. Methyl 2-benzyloxy-4-(4-methoxy)benzyloxybenzoate (4h)
Mp (MeOH) 66–67 ꢀC. IR (neat): nmax 2949, 1720, 1605, 1514,
1604, 1577, 1454, 1435, 1252, 1135 cmꢁ1. 1H NMR (200 MHz, CDCl3):
d
1.29 (d, J¼6.0 Hz, 6H), 3.83 (s, 3H), 4.42 (sept, J¼6.0 Hz, 1H), 6.41–
1245, 1172 cmꢁ1. 1H NMR (200 MHz, CDCl3):
d
3.82 (s, 3H), 3.87 (s,
6.45 (m, 2H), 7.58 (apparent br s, 1H), 7.73 (d, J¼8.8 Hz, 1H). 13C
3H), 4.99 (s, 2H), 5.14 (s, 2H), 6.53–6.65 (m, 2H), 6.92 (d, J¼8.0 Hz,
NMR (50 MHz, CDCl3): d 21.8, 51.8, 71.6, 102.3, 107.7, 112.0, 133.9,
2H), 7.28–7.57 (m, 7H), 7.89 (d, J¼9.4 Hz, 1H). 13C NMR (50 MHz,
160.2, 161.7, 167.3. LRMS (EI) m/z (rel intensity) 211 (MþHþ, 11), 210
(Mþ, 99), 168 (83), 137 (50), 136 (100), 108 (43). TOF-HRMS calcd for
C11H15O4 (MþHþ) 211.0965, found 211.0961.
CDCl3):
d 51.6, 55.3, 70.0, 70.6, 101.5, 106.1, 113.1, 114.1, 126.8, 127.7,
128.2, 128.5, 129.3, 133.9, 136.7, 159.7, 160.2, 163.3, 166.2. LRMS (EI)
m/z (rel intensity) 378 (Mþ, 3), 211 (16), 121 (100), 91 (20). TOF-
HRMS calcd for C23H23O5 (MþHþ) 379.1540, found 379.1546.
4.5.2. Methyl 2-benzyloxy-4-hydroxybenzoate (5b)
Mp (MeOH) 138–140 ꢀC. IR (neat): nmax 3311 (br), 1689, 1579,
4.4.9. Methyl 2-methoxymethyloxy-4-(4-methoxy)benzyloxy-
benzoate (4i)
1243, 1088 cmꢁ1. 1H NMR (200 MHz, CDCl3):
d 3.86 (s, 3H), 5.09 (s,
2H), 6.43 (d, J¼8.8 Hz, 1H), 6.46 (s, 1H), 7.22–7.54 (m, 5H), 7.78 (d,
Mp (MeOH) 50–52 ꢀC. IR (neat): nmax 2925, 1722, 1606, 1515,
J¼8.8 Hz, 1H). 13C NMR (50 MHz, CDCl3):
d 51.7, 70.2, 101.1, 107.7,
1245, 1094 cmꢁ1. 1H NMR (200 MHz, CDCl3):
d
3.51 (s, 3H), 3.80 (s,
111.2, 126.7, 127.7, 128.4, 134.0, 136.5, 160.6, 162.0, 166.8. LRMS (EI)
m/z (rel intensity) 258 (Mþ, 7), 226 (31), 91 (100). TOF-HRMS calcd
for C15H15O4 (MþHþ) 259.0965, found 259.0958.
3H), 3.85 (s, 3H), 4.99 (s, 2H), 5.23 (s, 2H), 6.62 (dd, J¼8.8, 2.2 Hz,
1H), 6.81 (d, J¼2.2 Hz, 1H), 6.91 (d, J¼8.8 Hz, 2H), 7.35 (d, J¼8.8 Hz,
2H), 7.83 (d, J¼8.8 Hz, 1H). 13C NMR (50 MHz, CDCl3):
d 51.6, 55.2,
56.3, 69.9, 95.0, 103.3, 107.4, 113.3, 113.9, 128.0, 129.3, 133.3, 158.8,
159.5, 163.0, 165.9. LRMS (EI) m/z (rel intensity) 332 (Mþ, 0.4), 121
(100). TOF-HRMS calcd for C18H21O6 (MþHþ) 333.1333, found
333.1334.
4.6. Preparation of the benzamides 6a and b
4.6.1. 2-Benzyloxy-N,N-diethyl-4-isopropoxybenzamide (6a)
A 10 mL microwave vessel was charged with the methyl benzoate
4a (0.60 g, 2.0 mmol), N,N-diethylamine (1.45 mL, 14.0 mmol),
Me3Al (2.0 M in toluene,1.5 mL, 3.0 mmol) and THF (2 mL) at rt. The
vessel was sealed and heated in the microwave reactor at 100 ꢀC
and 100 psi with the power set at 100 W for 45 min. At that time,
the reaction was quenched with 2 N HCl and the mixture was
extracted with EtOAc (3ꢂ10 mL). The combined organic layers were
washed with brine, dried over Na2SO4, filtered and concentrated
under reduced pressure to give the crude product. Further purifi-
cation of the crude by column chromatography on silica (30%
EtOAc/hexanes) furnished the desired product as a colourless oil
(0.68 g, 2.0 mmol, 99%). IR (neat): nmax 2975, 1630, 1429, 1276,
4.4.10. Methyl 2-isopropoxy-4-methoxymethyloxybenzoate (4j)
IR (neat): nmax 2977, 1727, 1605, 1576, 1499, 1436, 1245 cmꢁ1. 1H
NMR (200 MHz, CDCl3):
3H), 4.55 (sept, J¼6.2 Hz, 1H), 5.19 (s, 2H), 6.57–6.66 (m, 2H), 7.74–
7.83 (m, 1H). 13C NMR (50 MHz, CDCl3):
22.0, 51.5, 56.2, 71.9, 94.2,
d
1.38 (d, J¼6.2 Hz, 6H), 3.48 (s, 3H), 3.84 (s,
d
103.8, 107.5, 115.0, 133.4, 159.7, 161.5, 166.3. LRMS (EI) m/z (rel in-
tensity) 255 (MþHþ, 52), 254 (Mþ, 100), 223 (24). TOF-HRMS calcd
for C13H19O5 (MþHþ) 255.1227, found 255.1223.
4.4.11. Methyl 2-benzyloxy-4-methoxymethyloxybenzoate (4k)
IR (neat): nmax 2951, 1722, 1605, 1436, 1247, 1139 cmꢁ1. 1H NMR
1175 cmꢁ1. 1H NMR (400 MHz, CDCl3):
(t, J¼7.1 Hz, 3H),1.33 (d, J¼6.0 Hz, 6H), 3.10–3.40 (br m, 3H), 3.79 (br
s, 1H), 4.54 (sept, J¼6.0 Hz, 1H), 5.05 (s, 2H), 6.49–6.53 (m, 2H),
7.13–7.17 (m, 1H), 7.29–7.41 (m, 5H). 13C NMR (100 MHz, CDCl3):
d
0.99 (t, J¼7.1 Hz, 3H), 1.15
(200 MHz, CDCl3):
d
3.46 (s, 3H), 3.87 (s, 3H), 5.16 (s, 2H), 5.17 (s,
2H), 6.66 (dd, J¼10.2, 2.2 Hz, 1H), 6.69 (d, J¼2.2 Hz, 1H), 7.20–7.58
(m, 5H), 7.86 (d, J¼10.2 Hz, 1H). 13C NMR (50 MHz, CDCl3):
d 51.7,