1723
A. Regev et al.
Paper
Synthesis
1H NMR (500 MHz, CDCl3): δ = 7.56 (dd, J = 1.2, 7.9 Hz, 1 H), 7.14 (dd,
J = 1.2, 7.9 Hz, 1 H), 6.88 (dd, J = 1.2, 7.9 Hz, 1 H), 6.72 (dd, J = 1.2, 7.9
Hz, 1 H), 4.28 (m, 2 H), 2.91 (ddd, J = 5.9, 11.1, 13.0 Hz, 1 H), 2.51 (m, 2
H), 2.39 (ddd, J = 5.9, 11.1, 13.0 Hz, 1 H), 2.03 (m, 1 H), 1.94 (m, 1 H),
1.85 (m, 1 H), 1.64 (m, 1 H), 1.23 (t, J = 7.1 Hz, 3 H).
1H NMR (400 MHz, CDCl3): δ = 7.77 (dd, J = 1.2, 7.6 Hz, 1 H), 7.14 (m, 1
H), 6.71 (dd, J = 1.2, 7.6 Hz, 1 H), 6.60 (dd, J = 1.2, 7.6 Hz, 1 H), 4.23 (m,
2 H), 2.95 (ddd, J = 5.8, 10.7, 13.0 Hz, 1 H), 2.50 (m, 2 H), 2.36 (ddd,
J = 5.8, 10.7, 13.0 Hz, 1 H), 2.01 (m, 1 H), 1.84 (m, 1 H), 1.61 (m, 2 H),
1.18 (t, J = 7.1 Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ = 204.7, 168.9, 151.4, 133.7, 127.9,
13C NMR (100 MHz, CDCl3): δ = 204.8, 168.8, 153.8, 139.9, 128.9,
123.4, 117.3, 113.8, 88.1, 62.1, 39.7, 35.5, 27.7, 20.3, 14.0.
123.9, 115.9, 88.3, 88.0, 62.1, 39.8, 35.7, 27.7, 20.5, 14.0.
HRMS (ESI): m/z [M + Na]+ calcd for C15H17BrNaO4: 363.0202 and
HRMS (ESI): m/z [M + Na]+ calcd for C15H17INaO4: 411.0064; found:
365.0182; found: 363.0197 and 365.0174.
411.0058.
Ethyl 7-Bromo-2-hydroxy-2,3-dimethyl-2,3-dihydro-1-benzofu-
ran-3-carboxylate (8e)
Ethyl 2-Hydroxy-7-iodo-2,3-dimethyl-2,3-dihydro-1-benzofuran-
3-carboxylate (8f)
Prepared from ethyl 2-methyl-3-oxobutanoate (7, 54 mg, 0.38 mmol)
and 2-bromophenol (1e, 43 mg, 0.25 mmol). The crude compound
was purified by column chromatography [silica gel (230–400 mesh),
EtOAc–hexane (8:100)] to give a yellow oil; yield: 18 mg (23%).
Prepared from ethyl 2-methyl-3-oxobutanoate (7, 54 mg, 0.38 mmol)
and 2-iodophenol (1f, 55 mg, 0.25 mmol). The crude compound was
purified by column chromatography [silica gel (230–400 mesh),
EtOAc–hexane (8:100)] to give a yellow oil; yield: 8 mg (9%).
1H NMR (500 MHz, CDCl3): δ (mixture of diastereomers) = 7.35 (d,
J = 7.8 Hz, 1 H), 7.26 (d, J = 7.8 Hz, 1 H), 6.85 (t, J = 7.8 Hz, 1 H), 4.26
(m, 2 H), 1.79 (s, 3 H), 1.50 (s, 3 H), 1.30 (t, J = 7.1 Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ = 171.9, 154.1, 132.1, 132.0, 124.7,
122.8, 111.5, 103.5, 61.7, 59.4, 22.8, 21.9, 14.0.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 7.52 (dd,
J = 1.1, 7.8 Hz, 1 H), 7.25 (dd, J = 1.1, 7.8 Hz, 1 H), 6.71 (t, J = 7.8 Hz, 1
H), 4.23 (m, 2 H), 4.00 (s, OH), 1.75 (s, 3 H), 1.46 (s, 3 H), 1.27 (t, J = 7.1
Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ = 172.0, 157.2, 137.8, 130.8, 125.6,
124.1, 123.3, 110.9, 61.7, 59.8, 22.8, 21.9, 14.0.
HRMS (ESI): m/z [M + H]+ calcd for C13H16IO4: 363.0088; found:
HRMS (ESI): m/z [M + Na]+ calcd for C13H15BrNaO4: 337.0046 and
339.0026; found: 337.0044 and 339.0020.
363.0089.
Ethyl 2-(2-Bromophenoxy)-2-methyl-3-oxobutanoate (9e)
Ethyl 2-(2-Iodophenoxy)-2-methyl-3-oxobutanoate (9f)
The crude residue was purified by column chromatography [silica gel
(230–400 mesh), EtOAc–hexane (2.5:100)] to give a yellow oil; yield:
50 mg (63%).
1H NMR (500 MHz, CDCl3): δ = 7.58 (dd, J = 1.5, 7.9 Hz, 1 H), 7.20 (dd,
J = 1.5, 7.9 Hz, 1 H), 6.93 (dd, J = 1.5, 7.9 Hz, 1 H), 6.84 (dd, J = 1.5, 7.9
Hz, 1 H), 4.26 (q, J = 7.1 Hz, 2 H), 2.58 (s, 3 H), 1.63 (s, 3 H), 1.24 (t,
J = 7.1 Hz, 3 H).
The crude residue was purified by column chromatography [silica gel
(230–400 mesh), EtOAc–hexane (1:40)] to give a yellow oil; yield: 55
mg (60%).
1H NMR (400 MHz, CDCl3): δ = 7.79 (dd, J = 1.6, 7.8 Hz, 1 H), 7.19 (ddd,
J = 1.6, 7.8, 8.4 Hz, 1 H), 6.75 (m, 2 H), 4.23 (dq, J = 1.1, 7.1 Hz, 2 H),
2.60 (s, 3 H), 1.63 (s, 3 H), 1.20 (t, J = 7.1 Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ = 204.6, 169.0, 151.5, 133.8, 128.2,
13C NMR (100 MHz, CDCl3): δ = 204.4, 168.9, 154.0, 140.1, 129.2,
124.2, 118.5, 115.5, 88.3, 62.4, 26.0, 18.2, 13.9.
124.5, 116.9, 89.6, 88.4, 62.5, 26.6, 18.2, 13.9.
HRMS (ESI): m/z [M + Na]+ calcd for C13H15BrNaO4: 337.0046 and
HRMS (ESI): m/z [M + Na]+ calcd for C13H15INaO4: 384.9907; found:
339.0026; found: 337.0042 and 339.0017.
384.9897.
Ethyl 3-Chloro-5a-hydroxy-6,7,8,9-tetrahydrodibenzo[b,d]furan-
9a(5aH)-carboxylate (5g)
Ethyl 5a-Hydroxy-4-iodo-6,7,8,9-tetrahydrodibenzo[b,d]furan-
9a(5aH)-carboxylate (5f)
Ethyl 2-oxocyclohexanecarboxylate (4, 64 mg, 0.38 mmol) and 3-
chlorophenol (1g, 32 mg, 0.25 mmol). The crude compound was puri-
fied by column chromatography [silica gel (230–400 mesh), EtOAc–
hexane (8:100)] to give a yellow oil; yield: 32 mg (43%).
1H NMR (400 MHz, CDCl3): δ = 7.20 (d, J = 8.0 Hz, 1 H), 6.89 (d, J = 8.0
Hz, 1 H), 6.83 (s, 1 H), 5.37 (s, OH), 4.19 (m, 2 H), 2.12 (m, 1 H), 1.99
(m, 2 H), 1.82 (m, 1 H), 1.62 (m, 2 H), 1.51 (m, 1 H), 1.38 (m, 1 H), 1.25
(t, J = 7.1 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 173.2, 157.6, 134.5, 129.1, 125.5,
121.4, 111.8, 110.9, 61.8, 56.2, 33.8, 33.6, 21.6, 20.8, 14.0.
HRMS (ESI): m/z [M + Na]+ calcd for C15H17ClNaO4: 319.0708 and
321.0678; found: 319.0708 and 321.06741.
Prepared from ethyl 2-oxocyclohexanecarboxylate (4, 64 mg, 0.38
mmol) and 2-iodophenol (1f, 55 mg, 0.25 mmol). The crude com-
pound was purified by column chromatography [silica gel (230–400
mesh), EtOAc–hexane (1:20)] to give yellow oil; yield: 22 mg (23%).
1H NMR (400 MHz, CDCl3): δ = 7.51 (d, J = 7.8 Hz, 1 H), 7.25 (d, J = 7.8
Hz, 1 H), 6.68 (t, J = 7.8 Hz, 1 H), 5.33 (s, OH), 4.19 (m, 2 H), 2.05 (m, 3
H), 1.82 (m, 1 H), 1.63 (m, 2 H), 1.55 (m, 1 H), 1.39 (m, 1 H), 1.24 (t,
J = 7.1 Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ = 173.0, 157.6, 137.9, 130.6, 124.8,
123.0, 110.2, 75.4, 61.7, 57.8, 33.8, 33.7, 21.6, 20.8, 14.0.
HRMS (ESI): m/z [M + Na]+ calcd for C15H17INaO4: 411.0064; found:
411.0063.
Ethyl 1-(3-Chlorophenoxy)-2-oxocyclohexanecarboxylate (6g)
Ethyl 1-(3-Iodophenoxy)-2-oxocyclohexanecarboxylate (6f)
The crude residue was purified by column chromatography [silica gel
(230–400 mesh), EtOAc–hexane (1:20)] to give a yellow oil; yield: 7
mg (10%).
The crude residue was purified by column chromatography [silica gel
(230–400 mesh), EtOAc–hexane (1:40)] to give a yellow oil; yield: 55
mg (57%).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 1716–1725