240
Stach, Havlíček, Plaček, Rádl:
tert-Butyl (4R,6R)-6-{2-[2-Isopropyl-4,5-diph en yl-3-(ph en ylcarbam oyl)-
pyrrol-1-yl]eth yl}-2,2-dim eth yl-1,3-dioxan e-4-acetate (24)
A m ixture of diketon e 23 (2.33 g, 5.83 m m ol), am in e 3 (1.9 g, 7.1 m m ol) an d pivalic acid
(0.72 g, 7.1 m m ol) was refluxed in a m ixture of h eptan e (40 m l) an d toluen e (5 m l) for 30 h .
Th e m ixture was th en evaporated an d th e residue crystallized from propan -2-ol to give 23
(2.23 g, 60%) as a wh ite solid, m .p. 127–132 °C. 1H NMR (500 MHz, CDCl3, 25 °C): 7.28 m ,
2 H (4-Ph H-2); 7.26 m , 1 H (4-Ph H-4); 7.20 m , 2 H (5-Ph H-2); 7.19 m , 2 H (4-Ph H-3);
7.17 m , 2 H (an ilide H-3); 7.16 m , 2 H (5-Ph H-3); 7.14 m , 1 H (5-Ph H-4); 7.07 d, 2 H, J =
8.8 (an ilide H-2); 6.97 m , 1 H (an ilide H-4); 4.13 m , 1 H (dioxan e H-4); 4.07 m , 1 H
(NCH2CH2); 3.87 m , 1 H (NCH2CH2); 3.65 m , 1 H (dioxan e H-6); 3.62 sept, 1 H, J = 7.4
[CH(CH3)2]; 2.37 dd, 1 H, J = 15.2, 6.9 (CH2COO); 2.21 dd, 1 H, J = 15.2, 6.2 (CH2COO);
1.67 m , 2 H (NCH2CH2); 1.54 d, 3 H, J = 7.5 [CH(CH3)2]; 1.53 d, 3 H, J = 7.5 [CH(CH3)2];
1.48 m , 2 H (dioxan e H-5); 1.44 s, 9 H [C(CH3)3]; 1.34 s, 3 H [C(CH3)2]; 1.28 s, 3 H
[C(CH3)2]. 13C NMR (125 MHz, CDCl3, 25 °C): 170.2 (COO); 164.9 (CONH); 141.5 (pyrrole
C-2); 138.5 (an ilide C-1); 134.9 (4-Ph C-1); 132.3 (5-Ph C-1); 131.5 (2 C-2 of 5-Ph ); 130.6
(2 C-3 of 4-Ph ); 130.0 (pyrrole C-5); 128.6 (2 C-2 of 4-Ph ); 128.6 (2 C-3 of an ilide); 128.2
(2 C-3 of 5-Ph ); 126.7 (4-Ph C-4); 126.4 (5-Ph C-4); 123.4 (an ilide C-4); 121.5 (pyrrole C-4);
119.6 (2 C-2 of an ilide); 115.3 (pyrrole C-3); 98.6 (dioxan e C-2); 80.6 [C(CH3)3]; 66.5
(dioxan e C-6); 65.9 (dioxan e C-4); 40.9 (NCH2); 42.5 (CH2COO); 38.0 (NCH2CH2); 35.9
(dioxan e C-5); 28.1 [C(CH3)3]; 26.1[CH(CH3)2]; 21.7 [CH(CH3)2]; 21.6 [CH(CH3)2]; 19.7
[2 C(CH3)2]. IR: 1635 (C=O), 1710 (ester C=O). HR-MS: for C40H49N2O5 [M + H]+ calculated
637.3636 m/z, foun d 637.3641.
Calcium (3R,5R)-3,5-Dih ydroxy-7-[2-isopropyl-4,5-diph en yl-3-(ph en ylcarbam oyl)-
pyrrol-1-yl]h eptan oate (9)
A solution of h ydroch loric acid (10%; 3 m l) was added to a solution of com poun d 24 (1 g,
1.57 m m ol) in tetrah ydrofuran (15 m l), an d th e m ixture was stirred at 25 °C for 6 h . A solu-
tion of con cen trated sodium h ydroxide (40%; 2 m l) was th en added over 5 m in , m ain tain -
in g th e tem perature below 35 °C. Th e h eterogen eous m ixture form ed was vigorously stirred
for 15 h , an d th en poured in to a separatory fun n el con tain in g water (30 m l) an d h exan e
(10 m l). Th e organ ic layer was rem oved, an d th e aqueous layer extracted with a m ixture of
h exan e (8 m l) an d tetrah ydrofuran (2 m l). After com plete separation , th e aqueous layer was
extracted with eth yl acetate (3 × 8 m l), an d th e com bin ed eth yl acetate extracts were sh aken
with a solution of calcium acetate (20%; 3 × 1 m l). Th e resultin g eth yl acetate solution was
wash ed with water (2 × 1 m l), dried with an h ydrous calcium sulfate an d con cen trated in
vacuo to 4 m l. After filtration , th e clear solution was added dropwise durin g 5 m in to h ex-
an e (40 m l) un der vigorous stirrin g, an d th e m ixture was stirred for addition al 20 m in . Th e
precipitate was filtered off, wash ed with h exan e (20 m l) an d dried to give 0.54 g (62%) of 9
as a wh ite solid, m .p. 150 °C (dec.). 1H NMR (500 MHz, CD3OD, 25 °C): 7.33 m , 2 H (5-Ph
H-3); 7.3–6.9, 1 H (NH); 7.30 m , 1 H (an ilide H-4); 7.29 d, 2 H, J = 8.1 (an ilide H-2); 7.29 m ,
1 H (5-Ph H-4); 7.21 m , 2 H (4-Ph H-2); 7.21 m , 2 H (5-Ph H-2); 7.13 m , 2 H (4-Ph H-3);
7.06 m , 2 H (an ilide H-3); 7.02 m , 1 H (4-Ph H-4); 4.05 m , 1 H (CH2CH2CHOH); 3.95 m ,
1 H [CH(OH)CH2CHOH]; 3.93 m , 1 H (CH2CH2CHOH); 3.63 m , 1 H [CH(OH)CH2CHOH];
3.37 sept, 1 H, J = 7.1 [CH(CH3)2]; 2.29 dd, 1 H, J = 15.4, 3.8 (CH2CO); 2.19 dd, 1 H, J =
15.5, 8.7 (CH2CO); 1.67 m , 2 H (CH2CH2CHOH); 1.49 d, 3 H, J = 6.9 [CH(CH3)2]; 1.48 d,
3 H, J = 6.9 [CH(CH3)2]; 1.48 m , 1 H [CH(OH)CH2CHOH]; 1.33 m , 1 H [CH(OH)CH2CHOH].
Collect. Czech. Chem. Commun. 2008, Vol. 73, No. 2, pp. 229–246