J. O. Brower et al. / Tetrahedron 56 (2000) 7869±7883
7881
TFA followed by 1 mL of water. The dark solution was
stirred magnetically overnight at room temperature. The
solution was diluted with 15 mL of CH2Cl2, washed with
water (1£15 mL), saturated aqueous sodium bicarbonate
(2£15 mL) and brine (1£15 mL), dried (anhyd. MgSO4)
and ®ltered. The solution was concentrated (rotary evapora-
tor), and hexane was added to precipitate the product,
which was collected by ®ltration to yield 0.057 g of
pure off-white solid (68%). An analytical sample was
prepared by crystallization from methanol. It had mp
134±1358C; IR (KBr) n: 3184, 2952, 2867, 1707, 1597,
C37H48N4O6 (644.8): C, 68.92; H, 7.50; N, 8.69. Found: C,
69.10; H, 7.61; N, 8.51.
2-(p-Tosyl)-3-n-butyl-4-methyl-1H-pyrrole (13). To a
solution of p-tosylmethyl isocyanide (TosMIC) (11.18 g,
49.23 mmol) and 1,1,3,3-tetramethylguanidine (TMG)
(13 mL, 2.1 mol equiv.) in 50 mL of THF±2-propanol
(1:1 by vol) was added dropwise over a 1 h period of a
solution of 2-nitro-3-heptyl acetate (15) (10.0 g,
49.23 nmol) in 50 mL of THF±2-propanol (1:1). The
reddish solution was then stirred magnetically for three
days. The solution was then diluted with 100 mL of
CH2Cl2, washed with water (2£100 mL) and brine
(1£100 mL), dried (anhyd. MgSO4) and ®ltered. Removal
of the solvent (rotary evaporator) yielded a honey colored
oil. Crystallization from CH2Cl2±hexane yielded 14.3 g
(75%) of pure product. An analytical sample was prepared
by the addition of hexane to a CH2Cl2 solution of the pyrrole
to afford colorless crystals that were collected and dried
over P2O5 in a drying pistol overnight. They had mp 85±
868C and IR (KBr) n: 2955, 1636, 1457, 1307, 1229, 1189,
1
1456, 1396, 1312, 1226, 1135, 1083 cm21; H NMR d:
0.75 (3H, t, J6.3 Hz), 0.97±0.91 (4H, m), 2.11±1.92
(2H, m), 2.14 (3H, s), 2.41 (3H, s), 5.02 (1H, s), 6.53 (1H,
s), 7.30 (2H, d, J8.3 Hz), 7.67 (2H, d, J8.3 Hz) ppm; 13C
NMR d 173.06, 146.05, 143.07, 138.59, 130.88, 129.86,
129.68, 79.32, 30.12, 23.29, 22.50, 21.80, 13.98,
13.10 ppm. Anal. Calcd for C16H21NO3S (291.4): C,
62.52; H, 6.89; N, 4.56. Calcd. for C16H21NO3S´1/2
CH3OH (322.4): C, 61.46; H, 7.19; N, 4.34. Found: C,
61.77; H, 7.03; N, 4.29.
1144, 1089, 688, 590 cm21 1H NMR d: 0.87 (3H, t,
;
3-n-Butyl-4-methyl-3-pyrrolin-2-one (6).49 3-n-Butyl-4-
methyl-5-(p-tosyl)-3-pyrrolin-2-one (8) (0.100 g, 0.33
mmol) was dissolved in 6 mL of anhydrous ethanol; then
to the solution was added 0.0135 g (0.36 nmol) of NaBH4.
The clear solution was stirred at room temperature for
10 min. The NaBH4 was removed by gravity ®ltration and
the clear solution was washed with dilute acetic acid
(1£15 mL), water (2£15 mL) and brine (1£15 mL), extract-
ing each time with CH2Cl2. The solvent was removed by
rotary evaporation, yielding a white solid (0.045 g, 90.4%).
It had mp 89±908C [lit.49 mp 92±38C]; IR (KBr) n: 3206,
2950, 1682, 1558, 1540, 1456, 1395 cm21; 1H NMR d: 0.87
(3H, t, J6.8 Hz), 1.23 (2H, m), 1.39 (2H, m), 1.94 (3H, s),
2.21 (2H, t, J6.4 Hz), 3.77 (2H, s), 7.94 (1H, s) ppm; 13C
NMR d: 176.47, 149.12, 133.05, 80.61, 50.20, 30.81, 23.29,
22.79, 14.01, 13.31 ppm.
J6.3 Hz), 1.31 (4H, m), 1.95 (3H, s), 2.36 (3H, s), 2.58
(2H, t, J7.3 Hz), 6.68 (1H, d, J2.4 Hz), 7.23 (2H, d,
J8.3 Hz), 7.78 (2H, d, J8.3 Hz), 9.60 (1H, br. s) ppm;
13C NMR: 143.59, 140.89, 130.05, 129.83, 129.68, 129.10,
126.93, 121.11 ppm; MS: m/z (relative intensity) 291
[M1z](10), 230(7), 199(7), 136(20), 94(100) amu. Anal.
Calcd for C16H21NO2S (291.4): C, 65.95; H, 7.26; N, 4.81.
Found: C, 65.89; H, 7.41; N, 4.80.
2-(p-Tosyl)-3-n-butyl-4-methyl-5-bromo-1H-pyrrole (11).
2-(p-Tosyl)-3-butyl-4-methyl-1H-pyrrole (13) (6.77 g,
23.27 mmol) was dissolved in 50 mL of CH2Cl2 and chilled
to 08C in an ice bath. A solution of phenyltrimethylammo-
nium tribromide (PTT) (17.50 g, 46.54 mmol) dissolved in
50 mL CH2Cl2 was added dropwise over a 15 min period.
After the addition, the solution was stirred magnetically at
08C for 20 min. The solution was then washed with aqueous
sodium bisul®te solution (2£100 mL), water (1£100 mL),
and brine (1£100 mL). The solution was then dried (anhyd.
MgSO4), ®ltered, and the solvent removed (rotary evapora-
tor) to yield 8.61 g (100%) of a light brown solid product
that was suf®ciently pure for the next step. An analytical
sample was prepared by the addition of hexane to a CH2Cl2
solution of the pyrrole. The colorless crystals were collected
and dried over P2O5 in a drying pistol overnight. They had
mp 129±1308C and IR(KBr) n: 3300, 2958, 2859, 1595,
1455, 1371, 1308, 1289, 1204, 1166, 1141, 1110, 814,
Des-2,18-ethyl-2,18-di-n-butyl-mesobilirubin-IIIa (1). 3-
n-Butyl-4-methyl-3-pyrrolin-2-one (6) 0.38 g, 2.45 mmol
and 0.15 g (0.37 mmol) of dipyrrylmethane-dialdehyde (5)
was dissolved in ,60 mL of methanol and 20 mL of
aqueous 6 M KOH. After heating at re¯ux for 67 h in the
dark, the dark brown solution was poured into 150 mL of
water (with 30 mg of added ascorbic acid) and cooled in an
ice bath. The aqueous solution was acidi®ed with acetic
acid, which produced a brown precipitate, and centrifuged.
After centrifugation the liquid layers were decanted and the
solids ®ltered (sticky yellow-brown solid). The crude
product was then recrystallized from CH2Cl2±methanol
(three times) to yield a bright yellow solid (0.10 g,
42.7%). It had mp .3008C (dec.); IR (KBr) n: 3423,
2958, 2860, 1701, 1686, 1637, 1560, 1542, 1439, 1400,
1
715, 699, 652, 588, 526 cm21; H NMR d: 0.86 (3H, t,
J7.3 Hz), 1.31±1.22 (4H, m), 1.91 (3H, s), 2.40 (3H, s),
2.55 (2H, t, J7.8 Hz), 7.29 (2H, d, J8.3 Hz), 7.76 (2H, d,
J8.3 Hz), 8.86 (1H, br. s) ppm; 13C NMR d: 143.95,
140.10, 130.93, 129.94, 127.00, 124.54, 120.85, 105.37,
32.45, 24.84, 22.95, 21.66, 13.99, 10.01 ppm; MS: m/z (rela-
tive intensity) 371 [M1z](8), 327(8), 214(12), 172(100),
135(16), 91(16) amu. Anal. Calcd for C16H20NO2SBr
(370.3): C, 51.90; H, 5.43; N, 3.78. Found: C, 51.70; H,
5.73; N, 3.62.
1
1251, 1166, 1052, 1004, 936 cm21; H NMR d: 0.89 (3H,
t, J7.4 Hz), 0.31 (2H, m), 1.44 (2H, m), 2.06 (3H, s), 2.15
(3H, s), 2.29 (2H, t, J7.6 Hz), 2.56 (1H, ddd, J16.6, 2.3,
3.4 Hz), 2.79 (1H, ddd, J19.1, 2.3, 3.4 Hz), 2.88 (1H, ddd,
J14.8, 2.3, 19.1 Hz), 3.01 (1H, ddd, J14.8, 2.7 Hz), 4.07
(1H, s), 6.04 (1H, s), 9.15 (1H, s), 10.60 (1H, s), 13.65 (1H,
br. s). 13C NMR d: 179.73, 174.98, 142.42, 133.32, 129.77,
128.97, 124.37, 123.80, 119.58, 100.77, 32.87, 31.33, 23.36,
22.81, 22.45, 18.79, 14.13, 10.31, 9.91 ppm. Anal. Calcd for
3-Methyl-4-n-butyl-5-(p-tosyl)-3-pyrrolin-2-one (9). Freshly
prepared 2-(p-tosyl)-3-n-butyl-4-methyl-5-bromo-1H-pyr-
role (11) (0.859 g, 2.32 mmol) was dissolved in 20 mL