31.8, 31.5, 29.4, 29.3, 29.2, 22.6, 20.9, 14.0. MS: m/z (rel
intensity): 216 (100), 159 (2), 145 (2), 130 (4), 117 (99), 105 (9),
91 (7), 57 (4), 43 (21).
Exp er im en ta l Section
Gen er a l Meth od s. All reactions were carried out under Ar.
The solvents were purified by distillation over the drying agents
indicated and were transferred under Ar: THF, Et2O, DME
(Mg-anthracene), CH2Cl2 (CaH2), MeCN, Et3N, pyridine, NMP,
DMF (CaH2), MeOH (Mg), hexane, and toluene (Na/K). Flash
chromatography: Merck silica gel 60 (230-400 mesh). NMR:
chemical shifts (δ) are given in ppm relative to TMS, coupling
constants (J ) in Hz. Melting points are uncorrected. All com-
mercially available compounds were used as received.
2-(4-Octylp h en yl)eth a n ol (6b). A solution of acetate 6a
(11.62 g, 42 mmol) and NaOMe (227 mg, 4.2 mmol) in MeOH
(300 mL) was stirred for 8 h at ambient temperature. The solvent
was evaporated, and the residue was purified by flash chroma-
tography (10:1 f 4:1) to give alcohol 6b as a colorless syrup (9.15
g, 93%).17a 1H NMR (300 MHz, CDCl3): δ 7.12 (s, 4H), 3.83 (t, J
) 6.5, 2H), 2.83 (t, J ) 6.6, 2H), 2.57 (t + br s, J ) 7.6, 2H+OH),
1.59 (m, 2H), 1.4-1.2 (m, 10H), 0.88 (t, J ) 6.5, 3H). 13C NMR
(75 MHz, CDCl3): δ 141.1, 135.4, 128.9, 128.6, 63.7, 38.7, 35.5,
31.9, 31.5, 29.4, 29.3, 29.2, 22.6, 14.1. MS: m/z (rel intensity)
234 (M+, 17), 203 (18), 135 (25), 117 (23), 105 (100), 91 (33), 77
(10), 57 (12).
2-(4-Octylp h en yl)-1-iod oeth a n e (7). A solution of meth-
anesulfonyl chloride (2.51 g, 22 mmol) in CH2Cl2 (20 mL) was
added over 10 min to a solution of alcohol 6b (4.10 g, 17.5 mmol)
and Et3N (2.83 g, 28 mmol) in CH2Cl2 (80 mL). After being
stirred for 1 h, the reaction was quenched with aq satd NaHCO3,
the organic phase was dried (Na2SO4) and evaporated, and the
crude mesylate was dissolved in THF (120 mL). LiI (7.1 g, 53
mmol) was added, and the resulting mixture was stirred for 4 h
at ambient temperature. After evaporation of all volatile com-
ponents, the residue was suspended in hexane and the suspen-
sion was vigorously stirred for 5 min. The solid material was
Acetic Acid 2-(4-Hyd r oxyp h en yl)eth yl Ester (4). A sus-
pension of NaHSO4 on silica (4 g)20 and 2-(4-hydroxyphenyl)-
ethanol 3 (11.1 g, 80 mmol) in EtOAc (100 mL) and hexane (200
mL) was refluxed for 22 h. After that reaction time, additional
NaHSO4 on silica (1 g) was added and reflux was continued for
4 h. For workup, the solid material was filtered off and carefully
rinsed with Et2O (200 mL), the combined filtrates were evapo-
rated, and the residue was purified by flash chromatography
(hexanes/EtOAc, 10:1 f 4:1) to give acetate 4 as a colorless solid
(14.2 g, 98%).20 Mp ) 57-58 °C. H NMR (400 MHz, CDCl3): δ
1
7.06 (d, J ) 8.6, 2H), 6.77 (d, J ) 8.6, 2H), 5.56 (s, OH), 4.24 (t,
J ) 7.1, 2H), 2.86 (t, J ) 7.1, 2H), 2.05 (s, 3H). 13C NMR (100
MHz, CDCl3): δ 171.6, 154.4, 130.0, 129.6, 115.4, 65.3, 34.1, 21.0.
MS m/z (rel intensity): 180 (M+, <1), 120 (100), 107 (68), 91
(12), 77 (18), 65 (4), 51 (4), 43 (38).
Acetic Acid 2-[4-(Tr iflu or om eth a n esu lfon yloxy)p h en yl]-
eth yl Ester (5). A solution of triflic anhydride (26.7 g, 95 mmol)
in CH2Cl2 (30 mL) was added over a period of 1 h to a solution
of phenol 4 (14.2 g, 79 mmol) in CH2Cl2 (150 mL) and pyridine
(30 g) at 0 °C. After the addition was complete, stirring was
continued for 1 h at ambient temperature. For workup, the
reaction was quenched with aq satd NaHCO3, the aqueous layer
was repeatedly extracted with tert-butyl methyl ether, the
combined organic layers were dried over Na2SO4 and evaporated,
and the residue was dried in vacuo (10-3 Torr) to give analyti-
filtered off through
a short pad of silica, the filtrate was
evaporated, and the residue was dried in vacuo (10-3 Torr) to
give analytically pure iodide 7 as a colorless oil (5.37 g,
89%).17a 1H NMR (400 MHz, CDCl3): δ 7.14-7.05 (m, 4H), 3.32
(t, J ) 7.9, 2H), 3.14 (t, J ) 7.9), 2H), 2.56 (t, J ) 7.7, 2H), 1.59
(m, 2H), 1.38-1.18 (m, 10H), 0.87 (t, J ) 6.9, 3H). 13C NMR
(100 MHz, CDCl3): δ 141.6, 137.9, 128.6, 128.1, 40.1, 35.6, 31.9,
31.4, 29.5, 29.4, 29.3, 22.7, 14.1, 5.8. MS: m/z (rel intensity)
344 (M+, 7), 245 (8), 217 (100), 119 (50), 105 (7), 91 (10), 57 (5),
43 (5).
1
cally pure triflate 5 as a colorless syrup (23.2 g, 94%). H NMR
Dieth yl 2-Aceta m id o-2-[2-(4-octylp h en yl)eth yl]m a lon a te
(9). Diethyl 2-acetamidomalonate 8 (1.95 g, 9 mmol) was added
in portions to a solution of NaH (215 mg, 9 mmol) in DMF, and
the resulting mixture was stirred for 30 min until the evolu-
tion of H2 ceased. Iodide 7 (514 mg, 1.5 mmol) was then
introduced, and stirring was continued for 1 h at 50-60 °C (bath
temperature). The reaction was quenched with water, the
aqueous phase was repeatedly extracted with tert-butyl methyl
ether, the combined organic layers were dried (Na2SO4) and
evaporated, and the residue was purified by flash chromato-
graphy (hexanes, then hexanes/EtOAc, 1:1) to give product 9 as
a colorless solid (534 mg, 82%). Mp ) 58-59 °C (51-53 °C).17a
1H NMR (300 MHz, CDCl3): δ 7.10-7.01 (m, 4H), 6.76 (s, 1H),
4.20 (m, 4H), 2.68 (t, J ) 8.0, 2H), 2.55 (t, J ) 7.7, 2H), 2.45 (t,
J ) 8.0, 2H), 1 97 (s, 3H), 1.57 (m, 2H), 1.35-1.20 (m, 10H),
1.24 (t, J ) 7.2, 6H), 0.88 (t, J ) 7.0, 3H). 13C NMR: (75 MHz,
CDCl3): δ 169.0, 168.1, 140.7, 137.6, 128.36, 128.27, 66.4, 62.5,
35.5, 33.3, 31.9, 31.6, 29.7, 29.4, 29.3, 29.2, 22.9, 22.6, 14.1, 14.0.
MS: m/z (rel intensity) 433 (M+, <1), 388 (2), 318(2), 301 (2),
244 (2), 217 (93), 171 (100), 143 (15), 105 (14), 91 (5), 57 (5), 43
(14).
(400 MHz, CDCl3): δ 7.30 (d, J ) 8.7, 2H), 7.22 (d, J ) 8.7, 2H),
4.28 (t, J ) 6.8, 2H), 2.97 (t, J ) 6.8, 2H), 2.04 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ 170.8, 148.3, 138.5, 130.6, 121.6, 118.7,
64.2, 34.3, 20.8. MS m/z (rel intensity): 252 (41), 119 (100), 107
(9), 91 (21), 69 (13), 51 (4). Anal. Calcd for C11H11F3O5S: C, 42.31;
H, 3.55. Found: C, 42.36; H, 3.46.
Acetic Acid 2-(4-Octylp h en yl)eth yl Ester (6a ). A solution
of octylmagnesium bromide (0.63 M in THF, 45 mL) was added
over a period of 50 min to a solution of triflate 5 (7.23 g, 23.2
mmol) and Fe(acac)3 (818 mg, 2.32 mmol) in THF (150 mL) and
NMP (13.6 mL), causing an immediate color change from red to
dark brown/black and a slight increase of the reaction temper-
ature. After the solution was stirred for 30 min, additional
octylmagnesium bromide (20 mL), Fe(acac)3 (400 mg, 1.13
mmol), and NMP (4.5 mL) were added, and stirring was
continued for another 30 min. The reaction was then quenched
with aq HCl (1 M), the aqueous phase was repeatedly extracted
with tert-butyl methyl ether, the combined organic layers were
dried (Na2SO4) and evaporated, and the residue was purified
by flash chromatography (hexanes/EtOAc, 50:1 f 30:1) to give
product 6a as a colorless syrup (4.08 g, 64%).17a A second fraction
contains 2-(4-octylphenyl)ethanol 6b (1.1 g, 20%) formed as a
byproduct during the workup. Spectroscopic data of compound
6a : 1H NMR (300 MHz, CDCl3): δ 7.11 (s, 4H), 4.26 (t, J ) 7.2,
2H), 2.90 (t, J ) 7.6, 2H), 2.60 (t, J ) 7.6, 2H), 2.03 (s, 3H), 1.60
(m, 2H), 1.4-1.2 (m, 10H), 0.88 (t, J ) 6.7, 3H). 13C NMR (75
MHz, CDCl3): δ 170.9, 141.1, 134.8, 128.7, 128.5, 65.0, 35.5, 34.6,
Ack n ow led gm en t. Generous financial support by
the Deutsche Forschungsgemeinschaft (Leibniz award
to A.F.), the Fonds der Chemischen Industrie, and the
Merck Research Council is gratefully acknowledged.
J O049885D
3952 J . Org. Chem., Vol. 69, No. 11, 2004