dried over MgSO4. The solvent was removed in vacuo to give the
acid 4b as an oil; δH(200 MHz; CDCl3) 2.72 (2 H, d, J 6.6,
CH2CO2Et), 2.73 (1 H, dd, J 8.8 and 15.4, 3-H), 3.21 (1 H, dd,
J 8.8 and 15.4, 3-H), 4.16–4.31 (1 H, m, 2-H), 6.23 (1 H, br s,
NH), 6.65–6.79 (2 H, m) and 7.01–7.25 (2 H, m); m/z 177 (Mϩ,
13%), 130 (24), 118 (100) and 117 (38).
Method B. A solution of the ester 4a (1.15 g, 5.6 mmol) in
concentrated hydrochloric acid (30 cm3) was stirred for 1 h at
room temperature (RT). The solution was diluted with water
(20 cm3) and was stirred for a further 24 h. The solution was
evaporated to dryness and the solid residue was crystallised to
give the hydrochloride of compound 4b (0.72 g, 60%), mp
139 ЊC (from ethanol–light petroleum) (Found: C, 56.1; H, 5.7;
N, 6.5. C10H12ClNO2 requires C, 56.2; H, 5.7; N, 6.6%);
νmax(Nujol)/cmϪ1 2919 and 1714; δH(200 MHz; D2O) 3.03 (2 H,
d, J 8.8, CH2CO2Et), 3.06 (1 H, dd, J 8.2 and 16.5, 3-H), 3.48
(1 H, dd, J 8.2 and 16.5, 3-H), 4.50–4.57 (1 H, m, 2-H) and
7.36–7.44 (4 H, m); m/z 177 (Mϩ, 26%) and 118 (100).
(0.45 g, 1.4 mmol) in dichloromethane (4 cm3) at RT. After 3 h
the solution was poured into saturated aq. sodium hydrogen
carbonate (30 cm3). The mixture was extracted with dichloro-
methane (2 × 20 cm3) and the extracts were combined, dried
(MgSO4) and evaporated under reduced pressure. The residue
was purified by flash chromatography (dichloromethane) to
give the ester 9 (0.27 g, 88%) as an oil; δH(200 MHz; CDCl3)
1.27 (3 H, t, J 7.1), 1.60 (3 H, d, J 7.1), 3.93 (1 H, q, J 7.1), 4.19
(2 H, q, J 7.1), 6.35–6.37 (1 H, m, 3-H), 7.03–7.19 (1 H, m),
7.31–7.36 (1 H, m), 7.53–7.57 (1 H, m) and 8.56 (1 H, br s, NH).
Ethyl 2-(2,3-dihydro-1H-indol-2-yl)propanoates 10 and 11
(i) By route A. Sodium cyanoborohydride (0.55 g) was added
slowly in small portions to TFA (10 cm3) at 0 ЊC under N2.
After 15 min the ester 9 (0.35 g, 1.6 mmol) was added slowly.
The mixture was allowed to warm to RT and, after 1 h, add-
itional sodium cyanoborohydride (0.60 g) was added in por-
tions. The mixture was stirred for a further 1 h before water (30
cm3) was added. The resulting reaction mixture was added to
saturated aq. sodium hydrogen carbonate and the mixture was
extracted with dichloromethane (3 × 25 cm3). The organic
product was subjected to flash chromatography [dichloro-
methane–hexane (1:1)] to give the esters 10 and 11 (0.28 g,
79%) as an oil (Found: C, 71.5; H, 7.9; N, 6.5. C18H25NO4
requires C, 71.2; H, 7.8; N, 6.4%); νmax(film)/cmϪ1 3373 and
1724; δH(200 MHz; CDCl3) 1.22 (d, J 7.1, CHCH3 of 11), 1.23
(d, J 7.1, CHCH3 of 10), 1.26 (t, J 7.1, CH2CH3 of 10), 1.28 (t,
J 7.1, CH2CH3 of 11) (these four signals together, 6 H; ratio
10:11 = 1:1), 2.54–2.88 (2 H, m, 3-H and CHCH3), 3.14 (1 H,
dd, J 8.6 and 14.8, 3-H of both isomers), 3.95–4.11 (1 H, m,
2-H), 4.08–4.23 (2 H, m, CH2CH3), 6.57–6.71 (2 H, m) and
6.96–7.10 (2 H, m); m/z 233 (Mϩ, 6%) and 118 (100).
8,8a-Dihydroazeto[1,2-a]indol-2(1H)-one 1a
To a stirred suspension of the hydrochloride of 4b (0.21 g, 1.0
mmol) in dry acetonitrile (100 cm3) was added tris(2-oxo-
benzoxazolin-3-yl)phosphine oxide 5 (0.45 g, 1.0 mmol) and
dry triethylamine (0.41 g, 4.0 mmol). The reaction mixture was
heated under reflux for 6 h. The solvent was removed under
reduced pressure and the crude product was subjected to flash
chromatography (dichloromethane) and sublimation (70 ЊC
and 0.2 mmHg) to give 8,8a-dihydroazeto[1,2-a]indol-2(1H)-
one 1a (0.06 g, 37%), mp 77 ЊC (Found: C, 75.3; H, 5.7; N, 8.7.
C10H9NO requires C, 75.45; H, 5.7; N, 8.8%); νmax(Nujol)/cmϪ1
1773, 1645 and 1600; δH(200 MHz; CDCl3) 2.98 (1 H, dd, J 3.3
and 16.5, 1-H), 3.15 (1 H, dd, J 7.8 and 16.8, 8-H), 3.37 (1 H,
dd, J 8.8 and 16.8, 8-H), 3.53 (1 H, dd, J 5.2 and 16.5, 1-H),
4.32–4.44 (1 H, m, 8a-H) and 7.03–7.25 (4 H, m); m/z 159 (Mϩ,
33%) and 117 (100, Mϩ Ϫ CH2CO).
(ii) By route B. TFA (7 cm3) was added to a stirred solution of
the mixture of esters 12 and 13 (0.38 g, 1.2 mmol) in dichloro-
methane (4 cm3) at room temperature. After 3 h, the products
were poured into saturated aqueous sodium hydrogen carb-
onate (50 cm3). The organic products were extracted with
dichloromethane (3 × 40 cm3), and the extracts were combined,
dried (MgSO4) and evaporated under reduced pressure. Flash
chromatography gave (with dichloromethane) a mixture of the
esters 10 and 11 (0.23 g, 88%) as an oil νmax(film)/cmϪ1 3373 and
1724. The NMR spectrum showed the same signals as those in
the spectrum of the product from method (i) but in the ratio
10:11 = 5:1.
Ethyl 1-tert-butoxycarbonyl-1H-indole-2-acetate 6
To a stirred solution of ethyl 1H-indole-2-acetate 3 (0.51 g, 2.5
mmol) in dry dichloromethane (40 cm3) was added 4-dimethyl-
aminopyridine (0.31 g, 2.5 mmol) followed by di-tert-butyl
dicarbonate (0.82 g, 3.8 mmol). The solution was stirred at
room temperature for 3 h. Evaporation of the solvent followed
by flash chromatography [dichloromethane–hexane (1:1)] gave
the ester 6 as an oil (0.76 g, 100%) (Found: C, 67.7; H, 7.0; N,
4.6. C17H21NO4 requires C, 67.3; H, 7.0; N, 4.6%); νmax(film)/
cmϪ1 1734; δH(200 MHz; CDCl3) 1.25 (3 H, t, J 7.1), 1.66 (9 H,
s), 4.03 (2 H, s), 4.18 (2 H, q, J 7.1), 6.47 (1 H, s, 3-H), 7.19–7.28
(2 H, m), 7.47–7.52 (1 H, m) and 8.08 (1 H, d, J 8.8); m/z 303
(Mϩ, 16%) and 130 (100).
Ethyl 2-(1-tert-butoxycarbonyl-2,3-dihydro-1H-indol-2-yl)-
propanoates 12 and 13
The ester 7 (0.17 g, 0.5 mmol) in ethanol (4 cm3) and acetic
acid (0.5 cm3) was hydrogenated at 200 psi over rhodium
(5% on alumina, 300 mg). Flash chromatography gave (with
dichloromethane) a mixture of the esters 12 and 13 (0.15 g,
88%) as an oil (Found: C, 67.4; H, 7.9; N, 4.35. C18H25NO4
requires C, 67.7; H, 7.9; N, 4.4%); δH(200 MHz; CDCl3) 0.95 (3
H, t, J 7.2), 1.16 (3 H, d, J 7.2), 1.61 (9 H, s), 2.99 (1 H, dd, J 2.2
and 16.5, 3-H), 3.24 (1 H, dd, J 9.4 and 16.5, 3-H), 3.80 (2 H, q,
J 7.2), 3.59–4.19 (2 H, m), 6.86–6.94 (2 H, m), 7.08–7.16 (2 H,
m); m/z 319 (Mϩ, 2%), 219 (11) and 118 (100).
Ethyl 2-(1-tert-butoxycarbonyl-1H-indol-2-yl)propanoate 7
To a solution of the ester 6 (0.53 g, 1.7 mmol) in dry THF (5
cm3) at Ϫ78 ЊC was added slowly dropwise KHMDS (3.4 cm3,
0.5 in toluene, 1.7 mmol). After 1 h iodomethane (0.30 g, 2
mmol) was added dropwise. The reaction mixture was stirred
for 30 min then allowed to warm to RT. Saturated aq. ammon-
ium chloride was added and the organic components were
extracted with ether (3 × 30 cm3). The ether extracts were
washed with water (3 × 30 cm3) and brine (30 cm3) and dried
over MgSO4. The solvent was removed and the crude residue
was subjected to flash chromatography [dichloromethane–
hexane (1:1)] to give the ester 7 (0.51 g, 92%) as an oil (Found:
C, 68.3; H, 7.3; N, 4.4. C18H23NO4 requires C, 68.1; H, 7.3; N,
4.4%); νmax(film)/cmϪ1 3052, 1734 and 1453; δH(200 MHz;
CDCl3) 1.07 (3 H, t, J 7.1), 1.50 (3 H, d, J 7.1), 1.51 (9 H, s),
4.00 (2 H, q, J 7.1), 4.27 (1 H, q, J 7.1), 6.38 (1 H, s, 3-H), 6.99–
7.14 (2 H, m), 7.34 (1 H, dd, J 2.2 and 6.0) and 7.89 (1 H, dd,
J 2.2 and 7.1); m/z 317 (Mϩ, 7%) and 57 (100).
2-(2,3-Dihydro-1H-indolium-2-yl)propanoic acid
trifluoroacetates 14 and 15
(i) By route A. Potassium hydroxide (150 mg) dissolved in the
minimum amount of water was slowly added to a stirred sol-
ution of the 1:1 mixture of esters 10 and 11 (80 mg) in ethanol
(2 cm3). The reaction vessel was flushed with nitrogen and the
solution was stirred until the starting material could no longer
be detected by TLC. The ethanol was distilled off and the
remaining aqueous solution was extracted with ethyl acetate
(3 × 25 cm3). The extracts were combined, dried over MgSO4
and concentrated. The residue was then dissolved in TFA and
the excess TFA was removed by rotary evaporation to leave the
Ethyl 2-(1H-indol-2-yl)propanoate 918
TFA (0.5 cm3) was added to a stirred solution of the ester 8
1198
J. Chem. Soc., Perkin Trans. 1, 1998