Fleming et al.
331
above, together with signals from the minor isomer 27):
7.36–7.26 (3H, m, Ph), 7.13–7.12 (2H, m, Ph), 3.85 (2H, q,
J = 7.1, OCH2), 3.74 (1H, d, J = 11.0, PhCH), 3.10 (1H, dq,
J = 11.0 and 6.85, CHMe), 2.10 (6H, s, NMe2), 1.35 (3H, d,
J = 6.85, CHMe), and 0.91 (3H, t, J = 7.1, OCH2Me).
off under reduced pressure, and the residue was taken up in
distilled water (30 mL), washed with ether (4 × 10 mL),
acidified to pH 1 with aqueous hydrochloric acid (3 N,
~50 mL), and extracted with ether (4 × 15 mL). The com-
bined organic layers were washed with brine (15 mL), dried
(MgSO4), and the solvent evaporated off under reduced
pressure to give the acid (19) (3.2 g, 75% over two steps) as
an indeterminately low-melting solid. Rf(Et2O:light petro-
leum (bp 40–60 °C), 50:50) 0.43. IR νmax (film, cm–1): 1694
(C=O), 1593 (C=C), 840 (SiMe2), 732 (Ph), and 700 (Ph).
1H NMR (400 MHz, CDCl3) δ: 7.53–7.48 (2H, m, Ph), 7.51
(1H, d, J = 19, SiCH), 7.42–7.36 (3H, m, Ph), 6.29 (1H, d,
J = 19, CHCO), and 0.45 (6H, s, SiMe2). 13C NMR
(100 MHz, CDCl3) δ: 170.9+, 150.8–, 136.0+, 134.5–,
133.8–, 130.4–, 128.0–, and –3.6–. MS m/z (ESI): 229 (10%,
MNa+). Anal. calcd. for C11H14O2Si (%): C 64.0, H 6.8;
found: C 64.0 H 6.9. Benzylamine salt, mp 130 to 131 °C
(from MeOH). N.B. Upon addition of ether to the basic
aqueous solution, the formation of three layers was often ob-
served. The dark-coloured middle layer, presumably the
carboxylate salt, not completely soluble in the aqueous
layer, was combined with the lower aqueous layer, and car-
ried through in the acidification step. This problem was
worse when sodium hydroxide was used to hydrolyze the es-
ter, and largely avoided by using potassium hydroxide.
Ethyl 3-N,N-dimethylaminobutanoate (24)
Methyllithium (1.54 mol dm–3 in Et2O, 18.5 mL,
28.5 mmol) was added to 3-(E)-N,N-dimethylamino-
propenoate (2 g, 14 mmol) in dry ether (17 mL) at –15 °C
under nitrogen, maintaining the temperature below 0 °C. The
reaction was stirred at 0 °C for 30 min and then kept at room
temperature for 1 h. The reaction was quenched with ammo-
nium chloride solution (40 mL). The aqueous layer was ex-
tracted with ether (3 × 10 mL). The combined organic layers
were washed with brine, dried (MgSO4), and the solvent
evaporated under reduced pressure to give the amine (30)
1
(1.14g, 51%). IR νmax (film, cm–1): 1732 (C=O). H NMR
(400 MHz, CDCl3) δ: 4.13 (2H, q, J = 7.1, OCH2), 3.10 (1H,
ddq, J = 8.5, 5.7, and 6.6, CHMe), 2.53 (1H, dd, J = 14.4
and 5.7, CHACHBCO), 2.23 (6H, s, NMe2), 2.18 (1H, dd,
J = 14.4 and 8.5, CHACHBCO), 1.24 (3H, t, J 7.1,
OCH2Me), and 1.03 (3H, d, J = 6.6, CHMe).
Ethyl 3-N,N-dimethylamino-2-methylbutanoate (26)
Methyllithium (1.54 mol dm–3 in Et2O, 37 mL,
28.5 mmol)) was added to 3-(E)-N,N-dimethylamino-
propenoate (4 g, 28 mmol) in dry ether (34 mL) at –15 °C
under nitrogen, maintaining the temperature below 0 °C. The
reaction was stirred at –15 °C for 30 min and then kept at
room temperature for 16 h. The mixture was cooled to
–15 °C, methyl iodide (2.2 mL, 35 mmol) was added, and the
mixture kept at room temperature for 16 h. The reaction was
quenched with ammonium chloride solution (15 mL) and
water (10 mL). The aqueous layer was extracted with ether
(3 × 10 mL). The combined organic layers were washed
with brine and part of the solvent evaporated under reduced
pressure. The organic layer was washed with hydrochloric
acid solution (3 N), and the aqueous layer was washed with
ether (3 × 8 mL). The aqueous layer was basified with so-
dium hydroxide solution (10%), and extracted with ether (5
× 17 mL). The organic layer was washed with brine, dried
(MgSO4), and the solvent evaporated off to give the amine
(1.80 g, 37%) with only one diastereoisomer detectable, pre-
sumably the 2RS,3RS isomer by analogy with the formation
of the known compound 25. IR νmax (film, cm–1): 1735
N-{E-3-[Dimethyl(phenyl)silyl]propenoyl-(7R)-2,10-
camphorsultam (30)
Oxalyl chloride (2 mL, 23 mmol), was added to 3-(E)-
dimethyl(phenyl)silylpropenoic acid (3.2 g, 16 mmol) in di-
chloromethane (11 mL) under nitrogen at room temperature,
followed by N,N-dimethylformamide (0.55 mL), and the
mixture was stirred at this temperature until the bubbling
ceased (~1 h). The solvent and the excess oxalyl chloride
were evaporated off under reduced pressure at 50 °C and
then at 2 mmHg (1 mmHg = 133.322 Pa) for 2 h to give the
acid chloride 29. Meanwhile, n-butyllithium (1.6 mol L–1,
~10 mL) was added to (1R)-(+)-2,10-camphorsultam (31)
(3.23 g, 15 mmol) in THF (15 mL) under nitrogen at
−78 °C, using 1-pyreneacetic acid as the indicator. This so-
lution was added by cannula to the solution of the acid chlo-
ride 29 in THF (20 mL) at –78 °C, and the mixture stirred at
room temperature for 1 h. The mixture was filtered through
a silica pad, washing through with ether (50 mL). This fil-
trate was washed with sodium bicarbonate (30 mL), dried
(MgSO4), filtered and the solvent evaporated off under re-
duced pressure to give the crude product (5.694 g, 90%),
which was crystallized from ethanol (3.5 mL) to give a first
crop of the imide (2.23 g, 35% from the acid) as pale yellow
needles, mp 90 to 91 °C (from EtOH). The mother liquors
were then evaporated to give a second crop (0.14 g, 2%), mp
88.5–89.5 °C. The mother liquors were chromatographed
(SiO2, light petroleum (bp 40–60 °C) – Et2O, 9:1) to give a
third crop (0.765 g, 12%), mp 89.5–90 °C, making the total
1
(C=O) and 1155 (OC). H NMR (400 MHz, CDCl3) δ: 4.15
(2H, m, OCH2), 2.75 (1H, dq, J = 9.6 and 6.6, NCHMe),
2.51 (1H, dq, J = 9.6 and 6.9, COCHMe), 2.19 (6H, s,
NMe2), 1.09 (3H, d, J = 6.9, COCHMe), and 0.89 (3H, d,
J = 6.6, NCHMe). 13C NMR (100 MHz, CDCl3) δ: 176.1+,
61.8–, 59.8–, 44.6–, 40.6–, 14.2– and 8.5–. MS m/z (EI):
173 (30%, M+), 158 (20, M – Me), 128 (13, M – EtO), 73
(39, CO2Et), and 72 (100, Me2N=CHMe) (found: M+,
173.1411; C9H19NO2 requires M, 173.1416).
20
yield (3.13 g, 49%). [α]D +63.1 (c 1.04 in CHCl3).
Rf(Et2O–light petroleum (bp 40–60 °C), 50:50) 0.47. IR
3-(E)-Dimethyl(phenyl)silylpropenoic acid (28)
ν
max(Nujol, cm–1): 1672 (C=O), 1598 (C=C), 1166 (SO2N),
1
The crude ethyl 3-(E)-dimethy(phenyl)silylpropenoate
(15) (9.9 g) in methanol (40 mL) and potassium hydroxide
(10 g) in distilled water (9 mL) were stirred at room temper-
ature for 1.5 h. The methanol and ethanol were evaporated
and 1117 (SiPh). H NMR (250 MHz, CDCl3) δ: 7.52–7.50
(2H, m, Ph), 7.48 (1H, d, J = 18.2, SiCH), 7.36–7.35
(3H, m, Ph), 7.01 (1H, d, J = 18.2, CHCO), 3.93 (1H, dd,
J = 7.0 and 5.7, NCH), 3.50 (1H, d, J = 13.8, SO2CHAHB),
© 2004 NRC Canada