A suspension of ethyl 2-(4-benzenesulfonyl-1,3-dihydro-3-oxo-4H-furo[3,4-b]-indol-1-yl)propionate (10)
(62 mg, 0.15 mmol) in 3N NaOH solution and MeOH (1:2) (2 mL) was refluxed for 1 h. The mixture was
acidified with 10% hydrochloric acid, extracted with CH2Cl2. The extracts were washed with water, dried
over Na2SO4, concentrated to give a residue. The residue was treated with diazomethane to provide a crude
ester, which was purified by column chromatography (n-hexane : AcOEt = 5:1) to afford methyl 3-
propionylindol-2-carboxylate (12) (20 mg, 57%) as a pale yellow solid,, mp 98-99 °C (n-hexane-ether).
IR (Nujol) ν: 3302, 1725, 1644 cm-1; 1H-NMR (CDCl3) δ: 1.25 (3H, t, J = 7 Hz, CH2CH3), 3.08 (2H, q,
J = 7 Hz, CH2CH3), 3.98 (3H, s, OCH3), 7.20-7.97 (4H, m, aromatic protons), 9.26 (1H, br s, NH).
Anal. Calcd for C13H13NO3: C, 67.52; H, 5.67; N, 6.06. Found: C, 67.54; H, 5.74; N, 6.05.
Ethyl (E)-2-(1,3-dihydro-3-oxo-4H-furo[3,4-b]indol-1-ylidene)propionate (13)
To a solution of ethyl (E)-2-(4-benzenesulfonyl-1,3-dihydro-3-oxo-4H-furo[3,4-b]indol-1-ylidene)-
propionate (10) (411 mg, 1 mmol) in THF (40 mL) was added 1M TBAF in THF (1.0 mL, 1 mmol) at
-30°C and the mixture was stirred for 0.5 h. The reaction mixture was acidified with 1% hydrochloric acid
and extracted with CH2Cl2. The extracts were washed with water, dried over Na2SO4, and evaporated in
vacuo. The residue was separated by chromatography (CH2Cl2) to afford ethyl (E)-2-(1,3-dihydro-3-oxo-
4H-furo[3,4-b]indol-1-ylidene)propionate (13) (198 mg, 73%) as a pale yellow solid, mp 194-195°C (n-
1
hexane-AcOEt). IR (Nujol) ν: 3264, 1756 and 1635 cm-1; H-NMR (CDCl3) δ: 1.40 (3H, t, J = 7 Hz,
CH2CH3), 2.26 (3H, s, CH3), 4.43 (2H, q, J = 7 Hz, CH2CH3), 7.25-7.55 (3H, m, aromatic protons),
8.20 (1H, dd, J = 8, 0.5 Hz, H-4), 9.54 (1H, br s, NH). Anal. Calcd for C15H13NO4: C, 66.41; H,
4.83; N, 5.17. Found: C, 66.38; H, 4.89; N, 5.15.
Ethyl 2-(1,3-dihydro-3-oxo-4H-furo[3,4-b]indol-1-yl)propionate (14)
A suspension of ethyl (E)-2-(1,3-dihydro-3-oxo-4H-furo[3,4-b]indol-1-ylidene)propionate (13) (109 mg,
0.4 mmol) and 10% Pd-C (33 mg) in EtOH (12 mL) was stirred at 40°C for 1 h under hydrogen. The
catalyst was removed by filtration through Cerite and the filtrate evaporated off. The residue was purified
by chromatography (n-hexane : AcOEt = 3:1) to give ethyl 2-(1,3-dihydro-3-oxo-4H-furo[3,4-b]indol-1-
yl)propionate (14) (103 mg, 94%) as a white solid, mp 134-135°C (n-hexane-AcOEt). IR (Nujol) ν:
1
3242 and 1724 cm-1; H-NMR (CDCl3) δ: 1.28 (3H, d, J = 7 Hz, CHCH3), 1.31 (3H, t, J = 7 Hz,
CH2CH3), 3.14 (1H, dq, J = 7, 6 Hz, CHCH3), 4.29 (2H, q, J = 7, CH2CH3), 6.04 (1H, d, J = 6 Hz,
OCH), 7.20-7.68 (4H, m, aromatic protons), 10.06 (1H, br s, NH). Anal. Calcd for C15H15NO4: C,
65.92; H, 5.53; N, 5.13. Found: C, 65.93; H, 5.57; N, 5.14.
REFERENCES
1. E. D. Edstrom, ' Advances in Nitrogen Heterocycles’, Vol. 3, ed. by C. J. Moody, JAI Press,
London, 1998, p. 45; R. J. Sundberg, ' Comprehensive Heterocyclic Chemistry' , Pergamon Press,
New York, 1984, p. 374.
2. For reviews, see: S. J. Danishefsky and J. M. Schkeryantz, Synlett, 1995, 475.
3. For recent synthesis of pyrrolo[1,2-a]indoles and mitomycins, see: Z. Wang and L. S. Jimenez,
Tetrahedron Lett., 1996, 37, 6049; idem, J. Org. Chem., 1996, 61, 816; F. E. Ziegler and M. Y.
Berlin, Tetrahedron Lett., 1998, 39, 2455; W. Dong and L. S. Jimenez, J. Org. Chem., 1999, 64,