Compound 12b: bp 90–100 ЊC (0.35 mmHg) (Found: C, 65.9;
PF6
Me
N
Me
N
H, 9.3; N, 4.7. C16H27NO2Si requires C, 65.5; H, 9.3; N, 4.8%);
δH (270 MHz; CDCl3) 0.01 (9 H, s), 1.18 (3 H, t, J 7.3), 1.95 and
2.18 (2 H, ABq, J 15.2), 2.37 (3 H, s), 2.85 (1 H, dd, J 13.5, 5.9),
3.05 (1 H, dd, J 13.5, 8.9), 3.40 (1 H, dd, J 8.9, 5.9), 4.08 (2 H,
m) and 7.14–7.30 (5 H, m); νmax(film)/cmϪ1 2955, 1730 and 854.
CO2Et
i
CO2Et
CH2
SiMe3
21
22
Me
N
N,N-Dimethyl-N-cyanomethyl-á-(trimethylsilylbenzyl)-
ammonium bromide 13
CO2Et
Me
Me
+
A
solution of N,N-dimethyl-N-[α-(trimethylsilyl)benzyl]-
N
CO2Et
amine10 (950 mg, 4.6 mmol) and bromoacetonitrile (782 mg,
6.5 mmol) in DMF (10 cm3) was stirred at room temp. for 13 h.
The precipitated crystals were separated to give the title salt 13
(1.29 g, 85%), mp 188–189 ЊC (Found: C, 51.4; H, 7.0; N, 8.3.
C14H23BrN2Si requires C, 51.4; H, 7.1; N, 8.6%); δH (500
MHz; CDCl3) 0.32 (9 H, s), 3.42 (3 H, s), 3.69 (3 H, s), 4.90
and 5.14 (2 H, ABq, J 16.5), 4.93 (1 H, s), 7.42 (1 H, m),
7.54 (3 H, m) and 7.60 (1 H, m); νmax(KBr)/cmϪ1 1250 and
845.
24
23
+
(PhCH2)2
25
Scheme 4 Reagents and conditions: i, CsF, DMF, room temp., 3 h
tubing. CsF (912 mg, 6.0 mmol) was placed in the test tube. The
apparatus was dried under reduced pressure and flushed with
N2. DMF (10 cm3) was added to the flask with a syringe and
then CsF was added from the test tube. The mixture was stirred
for 3 h at 0 ЊC, room temp. or 60 ЊC (see Table 1), after which
it was quenched with 1% aqueous NaHCO3 (100 cm3) and
extracted with Et2O. The extract was washed with water, dried
(MgSO4), filtered and concentrated under reduced pressure.
The residue was distilled at 95–125 ЊC (0.6 mmHg) and the dis-
tillate (213 mg, 238 mg or 222 mg) was chromatographed on a
silica gel column with hexane–Et2O (1.5:1) as the eluent to give
N,N-dimethyl-α-cyano-2-methylbenzylamine2 3a, N-cyano-
methyl-N-methyl-2-methylbenzylamine 7a, N-(2-cyanoethyl)-
N-methylbenzylamine8 8a and N-methyl-N-trimethylsilyl-
methyl-α-cyano-2-methylbenzylamine 11a, which were purified
by redistillation. The product ratio was determined from the
Reaction of 13 with CsF
In a manner similar to that described for 5a, a mixture of 13
(333 mg, 1 mmol) and CsF (800 mg, 5.3 mmol) in DMF (10
cm3) was prepared and stirred at room temp. for 2 days, after
which it was quenched with water (200 cm3) and extracted with
Et2O (4 × 50 cm3) and EtOAc (3 × 50 cm3). The combined
extracts were extracted with 0.5 HCl (2 × 10 cm3). The acid
extract was washed with Et2O, made alkaline with Na2CO3 and
extracted with Et2O. The extract was washed with saturated
aqueous NaCl, dried (MgSO4) and concentrated under reduced
pressure. The residue was distilled to give 3-dimethylamino-3-
phenylpropiononitrile 15 (88 mg, 50%), bp 145–155 ЊC (7.5
mmHg) (Found: C, 75.4; H, 8.2; N, 16.0. C11H14N2 requires C,
75.8; H, 8.1; N, 16.1%); δH (500 MHz; CDCl3) 2.21 (6 H, s),
2.77 (1 H, dd, J 7.3, 17.1), 2.81 (1 H, dd, J 5.8, 17.1), 3.53 (1 H,
J 5.8, 7.3), 7.31 (3 H, m) and 7.36 (2 H, m); νmax(film)/cmϪ1 2240
and 700.
1
proton ratios of an H NMR spectrum of the mixture.
Compound 3a: bp 90–92 ЊC (0.4 mmHg); δH (270 MHz;
CDCl3) 2.31 (6 H, s), 2.39 (3 H, s), 4.84 (1 H, s) and 7.20–7.54
(4 H, m).
Compound 7a: bp 75–80 ЊC (0.5 mmHg) (Found: C, 75.6; H,
8.1; N, 15.9. C11H14N2 requires C, 75.8; H, 8.1; N, 16.1%);
δH (270 MHz; CDCl3) 2.36 (3 H, s), 2.43 (3 H, s), 3.42 (2 H, s),
3.59 (2 H, s) and 7.14–7.53 (4 H, m); νmax(film)/cmϪ1 2951, 2234,
1460, 1034 and 754.
Compound 8a: bp 115 ЊC (0.7 mmHg); the structure was
confirmed by comparison with an authentic sample prepared
from N-methylbenzylamine with 3-bromopropiononitrile.8
Compound 11a: bp 90–95 ЊC (0.3 mmHg) (Found: C, 68.1;
H, 9.1; N, 11.1. C14H22N2Si requires C, 68.2; H, 9.0; N, 11.4%);
δH (270 MHz; CDCl3) Ϫ0.01 (9 H, s), 1.93 and 2.04 (2 H, ABq,
J 14.0), 2.24 (3 H, s), 2.39 (3 H, s), 4.85 (1 H, s) and 7.18–7.53
(4 H, m); νmax(film)/cmϪ1 2957, 2230, 1250, 856 and 750.
N-[3-(Ethoxycarbonyl)propyl]-N-methyl-N-(trimethylsilyl-
methyl)benzylammonium hexafluorophosphate 21
A mixture of N-methyl-N-(trimethylsilyl)methylamine (5.90 g,
50 mmol), ethyl 4-bromobutyrate (9.81 g, 50 mmol) and K2CO3
(13.83 g, 100 mmol) in benzene (50 cm3) was heated at reflux for
20 h. The reaction mixture was then filtered and extracted with
1 HCl (100 cm3). The acid extract was washed with Et2O,
made alkaline with NaOH and extracted with Et2O. The extract
was washed with water, dried (MgSO4) and concentrated under
reduced pressure. The residue was distilled to give ethyl 4-
[methyl(trimethylsilylmethyl)amino]butyrate (9.59 g, 41.5%),
bp 75–77 ЊC (0.6 mmHg) (Found: C, 56.7; H, 10.9; N, 6.1.
C11H25NO2Si requires C, 57.1; H, 10.9; N, 6.1%); δH (270 MHz;
CDCl3) 0.05 (9 H, s), 1.26 (3 H, t, J 7.3), 1.76 (2 H, dt, J 6.9,
7.6), 1.86 (2 H, s), 2.19 (3 H, s), 2.30 (2 H, t, J 6.9), 2.33 (2 H, t,
J 7.6) and 4.12 (2 H, t, J 7.3); νmax(film)/cmϪ1 1738, 1250 and
856.
A solution of ethyl 4-[methyl(trimethylsilylmethyl)amino]-
butyrate (3.0 g, 13.0 mmol) and benzyl bromide (2.29 g, 13.0
mmol) in acetone (10 cm3) was heated at reflux for 20 h and
then evaporated in vacuo. The residue was added to a solution
of NH4PF6 (2.54 g, 15 mmol) in 50% aqueous MeOH (10 cm3),
stirred for 3 h and extracted with CHCl3 (4 × 50 cm3). The
extract was dried (MgSO4) and concentrated under reduced
pressure. The residue was recrystallized from EtOH to give the
title compound 21 (5.47 g, 96%), mp 116–117 ЊC (Found: C,
46.2; H, 7.1; N, 3.0. C18H32F6NO2PSi requires C, 46.2; H, 6.9;
N, 3.0%); δH (500 MHz; CDCl3) 0.29 (9 H, s), 1.25 (3 H, t, J 7.3),
2.17 (2 H, m), 2.46 (2 H, m), 2.98 (2 H, dd, J 18.3, 15.3), 2.99 (3
H, s), 3.32 (2 H, m), 4.13 (2 H, q, J 7.3), 4.41 (1 H, d, J 13.4),
4.46 (1 H, d, J 13.4) and 7.46–7.53 (5 H, m); νmax(Nujol)/cmϪ1
1736, 1260 and 841.
Reaction of 5b and CsF
In a manner similar to that described above, 5b (788 mg, 2
mmol) was treated with CsF (912 mg, 6 mmol) in DMF (10
cm3) at room temp. or 60 ЊC (see Table 1). The Et2O extract was
distilled at 90–115 ЊC (0.2 mmHg) and the distillate (281 mg or
302 mg) was chromatographed on a silica gel column with
hexane–Et2O (4:1) to give ethyl 2-dimethylamino-3-phenyl-
propionate9 4b, ethyl [methyl(2-methylbenzyl)amino]acetate 7b
and ethyl 2-[methyl(trimethylsilylmethyl)amino]-3-phenylpro-
pionate 12b, which were purified by redistillation. The product
1
ratio was determined from the proton ratios of an H NMR
spectrum of the mixture.
Compound 7b: bp 90–95 ЊC (0.35 mmHg) (Found: C, 70.2;
H, 8.5; N, 6.5. C13H19NO2 requires C, 70.5; H, 8.7; N, 6.3%);
δH (270 MHz; CDCl3) 1.27 (3 H, t, J 7.3), 2.37 (3 H, s), 2.38 (3
H, s), 3.26 (2 H, s), 3.66 (2 H, s), 4.16 (2 H, q, J 7.3) and 7.10–
7.30 (4 H, m); νmax(film)/cmϪ1 1738, 1182, 1046 and 745.
J. Chem. Soc., Perkin Trans. 1, 1997
27