Helvetica Chimica Acta Vol. 86 (2003)
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CH2Cl2 (2 ml) was added excess CH2N2 as a soln. in Et2O. The mixture was stirred briefly and then evaporated.
The resulting residue was purified by FC (AcOEt/hexane 1:1): 9 (70 mg, 99%). M.p. 175.28. IR (KBr): 1742,
1710, 1686, 1637. 1H-NMR ((D6)DMSO): 9.37 (s, 1 H); 8.22 8.15 (m, 4 H); 7.50 (2d, J 8.6, 4 H); 6.91 (d, J
1.9, 1 H); 6.85 (d, J 8.3, 1 H); 6.63 (dd, J 8.3, 1.9, 1 H); 6.04 (2s, 2 H); 5.90 (d, J 6.0, 1 H); 4.60 (d, J 8.3,
1 H); 4.05 (dd, J 8.3, 6.0, 1 H); 3.46 (s, 3 H). ES-MS (neg.): 532.1 ([M À H]À). ES-MS (pos.): 534.0 ([M
H] ), 556.0 ([M Na] ). Anal. calc. for C28H20ClNO8: C 62.99, H3.78, N 2.62; found: C 62.83, H3.86, N 2.61.
rel-(3R,4S,5R)-4-[(1,3-Benzodioxol-5-ylamino)carbonyl]-5-(4-chlorophenyl)-1',3',4,5-tetrahydro-1',3'-di-
oxospiro[furan-2(3H),2'-[2H]indene]-3-carboxylic Acid Sodium Salt (10). To a soln. of 5 (143 mg, 0.27 mmol)
in MeCN (27 ml) was added 0.02n NaOH(135 ml, 0.27 mmol) with a syringe pump over 1 h. After the addition
was completed, the mixture was stirred for an extra 2 h. The resulting soln. was concentrated and lyophilized: 10
(161 mg, 100%). White solid. M.p. 204.28. IR (KBr): 1744, 1707, 1660. 1H-NMR ((D6)DMSO): 9.91 (s, 1 H );
8.04 7.96 (m, 4 H); 7.38 (d, J 8.5, 2 H); 7.31 (d, J 8.5, 2 H); 7.09 (d, J 1.6, 1 H); 6.89 (dd, J 8.4, 1.6, 1 H);
6.83 (d, J 8.4, 1 H); 5.96 (s, 2 H); 5.71 (d, J 5.9, 1 H); 4.15 (d, J 8.7, 1 H); 3.65 (dd, J 8.7, 5.9, 1 H).
13C-NMR ((D6)DMSO): 202.0; 199.8; 169.1; 167.5; 146.8; 143.8; 142.7; 138.8; 137.2; 136.1; 135.8; 133.5; 131.8;
127.7; 123.4; 112.5; 107.8; 102.0; 100.8; 85.1; 83.0; 62.0; 56.7. ES-MS (neg.): 518.1 ([M À H]À). ES-MS (pos.):
520.0 ([M H] ), 542.0 ([M Na] ), 502.0 ([M À Na 2 H ] ).
rel-(3R,4S,5R)-4-[(1,3-Benzodioxol-5-ylamino)carbonyl]-5-(3,4-dichlorophenyl-1',3',4,5-tetrahydro-1',3'-
dioxospiro[fluran-2(3H),2'-[2H]indene]-3-carboxylic Acid Sodium Salt (11). As described for 10 with 26
(143 mg; 0.27 mmol): 11 (161 mg, 100%). White solid. IR (KBr): 3616 3100, 1745, 1708, 1661. 1H-NMR
((D6)DMSO): 10.02 (s, 1 H); 8.07 7.96 (m, 4 H); 7.59 (d, J 1.6, 1 H); 7.52 (d, J 8.6, 1 H); 7.35 (dd, J 8.3,
1.6, 1 H); 7.06 (d, J 1.9, 1 H); 6.83 (d, J 8.3, 1 H); 6.73 (dd, J 8.6, 1.9, 1 H); 5.96 (s, 2 H); 5.70 (d, J 5.7,
1 H); 4.13 (d, J 8.6, 1 H); 3.66 (dd, J 8.9, 6.0, 1 H). 13C-NMR ((D6)DMSO): 201.7; 199.5; 168.7; 167.3; 146.7;
143.7; 142.7; 138.8; 138.5; 137.0; 135.7; 133.3; 130.4; 139.8; 129.7; 127.8; 126.2; 123.4; 123.3; 112.6; 107.7; 102.0;
100.7; 84.3; 83.0; 61.9; 56.2. ES-MS (neg.): 552.1 ([M À H]À).
rel-(2R,3S,3aR)-5a-Amino-N-(1,3-benzodioxol-5-yl)-2-(4-chlorophenyl)-2,3,3a,4,5a,10-hexahydro-4,10-di-
oxofuro[2,3-c]indeno[1,2-b]furan-3-carboxamide (13). To a soln. of 5 (150 mg, 0.29 mmol) in MeCN (5 ml) was
added aq. NH4OHsoln. (0.5 ml). After 2 h, the mixture was evaporated and co-evaporated twice with benzene.
The resulting solid was triturated with AcOEt to give 13 (57 mg, 37%). White solid.(IR (KBr): 3068, 3013, 1723,
1
1679. H-NMR ((D6)DMSO): 10.02 (s, 1 H); 8.24 (d, J 7.9, 1 H); 8.15 (t, J 7.3, 1 H); 8.01 (d, J 7.9, 1 H);
7.90 (t, J 7.3, 1 H); 7.68 (d, J 8.0, 2 H); 7.57 (d, J 8.0, 2 H); 6.93 (d, J 7.9, 2 H); 6.70 (d, J 8.6, 1 H); 6.18
(d, J 5.8, 1 H); 6.14 (s, 2 H); 4.42 (d, J 9.2, 1 H); 4.28 (br. s, 2 H); 4.08 (dd, J 9.2, 5.8, 1 H). ES-MS (neg.):
517.9 ([M À H]À).
rel-(3R,3aS,6aR)-5-(4-Acetylphenyl)-3-(3,4-dichlorophenyl)-3a,6a-dihydrospiro[1H-furo[3,4-c]pyrrole-
1,2'-[2H]indene]-1',3',4,6(3H,5H)-tetrone (14). As described for 5, 14 was obtained in 40% yield. White solid.
1H-NMR ((D6)DMSO): 8.17 8.07 (m, 6 H); 7.76 7.75 (m, 1 H); 7.65 (d, J 8.6, 1 H); 7.47 (dd, J 8.2, 1.9,
1 H); 7.33 (d, J 8.3, 2 H); 6.11 (d, J 7.6, 1 H); 4.38 (t, J 7.9, 1 H); 4.24 (d, J 8.3, 1 H); 2.60 (s, 3 H). ES-MS
(neg.): 532.1 ([M À H]À), 550.1 ([M H2O À H]À). ES-MS (pos.): 552.2 ([M H2O H] ), 534.1 ([M H] ).
rel-(2R,3S,3aR)-N-(4-Acetylphenyl)-2-(3,4-dichlorophenyl)-2,3,3a,4,5a,10-hexahydro-5a-hydroxy-4,10-di-
oxofuro[2,3-c]indeno[1,2-b]furan-3-carboxamide (15). As described for 10, with 14 (100 mg, 0.19 mmol),
MeCN, and 0.02n NaOH(9.4 ml, 0.19 mmol). The lyophilizate was purified by reversed-phase semi-prep.
HPLC (gradient MeCN/H2O containing CH3COOH(0.06%)). The desired fractions were lyophilized: 15
1
(43 mg, 42%). White solid. IR (KBr): 3241, 1764, 1726, 1673. H-NMR ((D6)DMSO): 8.82 (s, 1 H); 7.99 7.93
(m, 2 H); 7.88 7.84 (m, 3 H); 7.77 7.75 (m, 1 H); 7.64 (s, 1 H); 7.43 (s, 2 H); 7.34 (s, 2 H); 7.34 (d, J 8.3, 2 H);
6.83 (s, 1 H); 6.08 (d, J 4.8, 1 H); 4.16 (d, J 8.6, 1 H); 3.99 (dd, J 8.5, 5.2, 1 H); 2.5 (s, 3 H). ES-MS (neg.):
549.9 ([M À H]À). ES-MS (pos.): 552.0 ([M H] ).
rel-(3R,4S,5R)-4-{[(4-Acetylphenyl)amino]carbonyl}-5-(3,4-dichlorophenyl)-1',3',4,5-tetrahydro-1',3'-di-
oxospiro[furan-2(3H),2'-[2H]indene]-3-carboxylic Acid Sodium Salt (16): As described for 10, with 14 (43 mg,
0.08 mmol), MeCN, and 0.02n NaOH(4 ml, 0.08 mmol). The lyophilizate was triturated with MeCN: 16 (28 mg,
62%). White solid. IR (KBr): 2900, 1710, 1591. 1H-NMR ((D6)DMSO): 10.53 (s, 1 H); 8.10 7.97 (m, 4 H); 7.89
(d, J 8.6, 2 H); 7.63 (d, J 8.9, 2 H); 7.58 7.57 (m, 1 H); 7.48 (d, J 8.3, 1 H); 7.35 7.33 (m, 1 H); 5.72 (d, J
5.7, 1 H); 4.16 (d, J 8.6, 1 H); 3.89 (dd, J 8.6, 5.7, 1 H); 2.45 (s, 3 H). ES-MS (neg.): 550.1 ([M À H]À). ES-
MS (pos.): 552.1 ([M H] ).
rel-(3R,3aS,6aR)-3-(4-Chlorophenyl)-3a,6a-dihydro-5-phenylspiro[1H-furo[3,4-c]pyrrol-1,2'-[2H-indene]-
1',3',4,6(3H,5H)-tetrone (17). As described for 5, 17 was obtained in 61% yield. White solid. M.p. 2098. IR
(KBr): 1774, 1750, 1717. 1H-NMR ((D6)DMSO): 8.15 8.08 (m, 4 H); 7.40 7.27 (m, 7 H); 7.22 (d, J 8.3, 2 H);
6.04 (dd, J 7.6, 1.6, 1 H); 4.55 (d, J 14.9, 1 H); 4.35 (d, J 14.9, 1 H); 4.18 4.13 (m, 2 H ). 13C-NMR