J. M. Sanderson et al. / Tetrahedron 61 (2005) 11244–11252
11251
˚
(5) (0.100 g, 0.44 mmol), AcOH (25 ml, 0.44 mmol) and 3 A
molecular sieves (powdered; 3 g) in DCE (4 ml) was stirred
under argon at room temperature for 17 h before the
addition of NaBH(OAc)3 (0.120 g, 0.57 mmol). After
stirring for a further 5.5 h, the mixture was filtered through
a porosity three sinter, and the sieves washed with CHCl3
(2!10 ml). The combined organic extracts were then
washed successively with NaOH solution (1 M aq; 25 ml)
and H2O (2!25 ml) before being dried (K2CO3), filtered
and concentrated in vacuo to give a green oil. Purification
using flash column chromatography (pentane/Et2O; 4:1)
gave the title compound (0.051 g, 23%) as a yellow oil. 1H
NMR (400 MHz, CDCl3); d 0.89–1.08 (4H, m), 1.24–1.80
(10H, m), 2.26–2.45 (4H, m), 2.79–2.80 (1H, m), 3.66 (3H,
s, –CO2Me), 3.73–3.79 (4H, m, MeOPh– and Me-CH(Ar)-
NH–), 6.80 (2H, d, JZ8.5 Hz, Ar), 7.01 (2H, d, JZ8.1 Hz,
Ar), 7.13 and 7.24 (2H, d, JZ8.3 Hz, Ar), 7.39 and 7.42
(2H, d, JZ8.3 Hz, Ar). 13C NMR (100 MHz, CDCl3); d
23.46, 26.30, 28.37, 29.55, 31.75, 33.51, 39.72, 41.00,
42.94, 51.50, 51.98, 55.18, 55.71, 113.46, 122.02 (q, JZ
67.8 Hz, –CF3), 126.38, 127.11, 128.40, 129.87, 131.28,
132.91, 149.32, 157.62, 174.40. n/cmK1 (liquid film) 3350
chromatography to give the title compound (5.23 g, 74%) as
a colourless oil. 1H NMR (300 MHz, CDCl3); d 1.31 (3H, d,
JZ6.6 Hz, Me-CH(Ar)-NH–), 1.42–1.83 (7H, m), 1.91–
2.12 (1H, m), 2.35–2.41 (3H, m), 2.60–2.82 (2H, m), 3.70
(3H, s, –CO2Me), 3.76 (1H, q, JZ6.5 Hz, Me-CH(Ar)-NH–),
3.91 (4H, br m, –OCH2CH2O–), 7.22–7.36 (5H, m, Ar).
n/cmK1 (liquid film); 3430 (w), 2960 (s), 1745 (s), 1440 (s),
1360 (s), 1160 (s), 1100 (s), 760 (m), 700 (s). [a] 3D0 C6 (c
0.4, CHCl3). m/z (EI, %): 347 (1, MC), 332 (11), 246 (5),
187 (100), 105 (63). C20H29NO4 requires: C, 69.1; H, 8.4; N,
4.0. Found: C, 68.7; H, 8.3; N, 3.8.
4.1.21. (10R,4aS,8aR)-3,4,4a,5,7,8,8a-Septahydro-6-
[spiro-(2,5-oxa)cyclopentyl]-1-[(10phenyl)ethyl]quinolin-
2(1H)-one. A solution 0of methyl (10R,1S,2R)-5-[spiro-(2,5-
oxa)cyclopentyl]-2-[1 -(phenylethyl)amino]cyclohexane-
propionate 15 (5.0 g, 14.4 mmol) in toluene (60 ml) and
acetic acid (20 ml) was heated at 70 8C for 15 h before the
solvents were removed in vacuo and the residue dissolved in
toluene (20 ml). After washing the organic solution
successively with sodium bicarbonate solution (satd aq;
20 ml), and water (2!20 ml), the solution was dried
(Na2SO4), filtered, and concentrated in vacuo. Purification
using chromatography (ether) gave the title compound
(2.9 g, 64%) as a colourless oil. 1H NMR (300 MHz,
CDCl3); d 1.21 (1H, t, JZ6.9 Hz), 1.25–1.72 (5H, m), 1.83–
2.02 (3H, m), 2.32–2.60 (4H, m), 2.96–3.03 (1H, m), 3.48
(1H, q, JZ7.8 Hz), 3.85 (2H, br d, JZ5.5 Hz, –OCH2CH2-
O–), 3.91 (2H, br d, JZ5.5 Hz, –OCH2CH2O–), 5.81 (1H, q,
JZ7.2 Hz, Me-CH(Ar)-NH–), 7.21–7.39 (5H, m, Ar).
n/cmK1 (liquid film) 2950 (m), 1630 (s), 1440 (m), 1380
(w), 1130 (s), 1100 (s), 945 (w), 700 (m). [a] 3D0 C38 (c 0.5,
CHCl3). m/z (EI, %): 315 (83, MC), 270 (8), 224 (14), 205
(14), 120 (31), 105 (100), 101 (73). C19H25NO3 requires: C,
72.3; H, 8.0; N, 4.4. Found: C, 72.3; H, 8.1; N, 4.3.
(w), 2920 (s), 1730 (s), 1610 (s), 1505 (s), 1445 (s), 1240 (s),
30
D
1180 (s), 1040 (m), 940 (m), 825 (m). [a]
C7 (c 0.1,
CHCl3). m/z (EI, %): 517 (4, MC), 489 (20), 474 (13), 240
(20), 200 (22), 185 (25), 149 (33), 121 (100). C28H34F3N3O3
requires: 517.255227. Found: 517.254865.
4.1.19. Methyl(10R,1S,2R,5S)-5-[(4-methoxyphenyl)
methyl]-2-{10-[3-(3-trifluoromethyl-3H-diazirin-3-yl)
phenyl]ethylamino}cyclohexanepropionate (12). The title
compound was prepared from (R)-1-[3-(3-trifluoromethyl-
3H-diazirin-3-yl)phenyl]ethylamine
(4)
(0.040 g,
0.175 mmol) and (G)-3-[2-oxo-5-(4-methoxybenzyl)cyclo-
hexyl]propionic acid methyl ester (6) (0.054 g, 0.177 mmol)
using the method described above for the preparation of
amine (13) (Section 4.1.8). Purification of the crude product
using flash column chromatography (pentane/Et2O; 4:1)
gave the title compound (0.023 g, 5%) as a pale yellow oil.
1H NMR (300 MHz, CDCl3); d 0.90–1.11 (4H, m), 1.22–
1.70 (10H, m), 2.30–2.49 (4H, m), 2.79–2.80 (1H, m), 3.63
(3H, s, –CO2Me), 3.72–3.80 (4H, m, MeOPh– and Me-
CH(Ar)-NH–), 6.81 (2H, d, JZ8.2 Hz, Ar), 7.03 (2H, d, JZ
8.5 Hz, Ar), 7.06–7.20 (1H, m, Ar), 7.31 and 7.40 (3H, m,
Ar). n/cmK1 (liquid film) 3350 (w), 2910 (s), 2850 (m),
1740 (s), 1615 (w), 1515 (s), 1250 (s), 1160 (s). [a] 3D0 K9 (c
0.1, CHCl3). m/z (EI, %): 517 (6, MC), 489 (5), 304 (5), 268
(21), 240 (12), 185 (24), 149 (34), 121 (100). C28H33F3N3O3
requires: 517.255227. Found: 517.254469.
4.1.22. (10R,4aS,8aR)-3,4,4a,5,7,8,8a-Heptahydro-1-[(10-
phenyl)ethyl]quinolin-2,6(1H)-dione (16). A solution of
(10R, 4aS, 8aR)-3,4,4a,5,7,8,8a-septa hydro-6-[spiro-(2,5-
oxa)cyclopentyl]-1-[(10phenyl)ethyl]quinolin-2(1H)-one
(2.5 g, 7.9 mmol) in acetic acid (40 ml) and water (40 ml)
was heated at 80 8C for 16 h before the solvents were
removed in vacuo and the residue dissolved in ether (20 ml).
After washing the organic layer successively with sodium
bicarbonate solution (satd aq; 20 ml) and water (2!20 ml),
the solution was dried (Na2SO4), filtered, and concentrated
in vacuo. Purification using chromatography (ether) gave
1
the title compound (1.77 g, 82%) as a colourless oil. H
NMR (300 MHz, CDCl3); d 1.25–1.44 (1H, m), 1.63 (3H, d,
JZ7.3 Hz, Me-CH(Ar)–NH–), 1.76 (1H, t, JZ7.9 Hz),
1.98–2.08 (1H, m), 2.14–2.32 (5H, m), 2.41–2.48 (1H, m),
2.55–2.61 (2H, m), 3.41–3.45 (1H, m), 6.04 (1H, q, JZ
7.1 Hz, Me-CH(Ar)-NH–), 7.27–7.44 (5H, m, Ar). n/cmK1
(liquid film) 2960 (s), 1715 (s), 1625 (s), 1445 (m), 1285
(m), 1205 (m), 700 (m). [a]3D0 C33 (c 0.6, CHCl3). m/z (EI,
4.1.20.
Methyl(10R,1S,2R)-5-[spiro-(2,5-oxa)cyclo-
pentyl]-2-[10-(phenylethyl)amino]cyclohexanepropio-
nate (15). A mixture of 4-toluenesulphonic acid (0.05 g,
0.3 mmol), (G) methyl (2,5-oxo)-5-[spiro-(2,5-oxa)cyclo-
pentyl]cyclohexane propionate (5.0 g, 20.6 mmol) and R(C)-
a-methylbenzylamine (2.62 g, 23.3 mmol) in toluene
(60 ml) was heated at reflux with a Dean-Stark water
separator for 23 h, before the solvent was removed in vacuo
and the residue dissolved in ethanol. To this was added
Raney nickel (prepared from 1 g of a slurry in water) and the
mixture stirred under an atmosphere of hydrogen for 6 days.
Following filtration of the mixture through a pad of silica,
the residue was concentrated in vacuo and purified using
%): 271 (100, MC), 256 (7), 174 (20), 160 (34), 105 (90).
12
C C13H21NO2
272.161027.
requires:
272.160584.
Found:
16
4.1.23. Dimethyl[4-(3-trifluoromethyl-3H-diazirin-3-yl)
phenyl]methyl phosphonate (18). A solution of 3-(a-
iodo-4-tolyl)-3-(trifluoromethyl)-3H-diazirine (17) (0.500 g,
1.53 mmol) in toluene (10 ml) and trimethylphosphite (2 ml,