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J. B. CAMPBELL AND J. W. FIROR
partitioned between the layers. The layers were separated and the aqueous phase was
extracted with an additional portion of ethyl acetate. The combined organic extracts
were washed with water and then brine. After drying (MgS04) and concentrating, the
crude product was purified by flash chromatography on silica gel using ethyl acetate–
hexanes (2:3) as the eluent. The product was obtained as a viscous oil, which solidi-
fied upon standing (17.4 g, 64 mmol, 96%); TLC, Rf ¼ 0.17, ethyl acetate–hexanes
(1:1); 1H NMR: (DMSO-d6) 0.83 (t, J ¼ 7.2 Hz, 3H), 1.47 (m, 2H), 2.57
(d, J ¼ 16.8 Hz, 1H), 2.76 (d, J ¼ 16.8 Hz, 1H), 3.19 (m, 2H), 3.35 (s, 2H), 4.83 (s,
2H), 6.76 (dd, J ¼ 7.6 Hz, 1H), 7.23 (d, J ¼ 7.6 Hz, 1H), 7.43 (d, J ¼ 7.6 Hz, 1H);
13C NMR (CDCl3): 11.1, 20.4, 44.1, 43.8, 58.2, 61.9, 85.0, 96.6, 118.1, 118.6,
119.5, 129.2, 131.5, 142.7, 170.2; MS 272 (mþ þ 1); IR (CBrCl3, cmꢂ1): 3350,
2970, 2230, 1685, 1603, 1505, 1315, 1145.
Preparation of 2-(1-Propyl-2-oxo-3-pyrrolin-4-yl)amino-3-
(chloromethyl)benzonitrile 7
A sample of 6 (6.31 g, 23.3 mmol) was mixed with triphenylphosphine (6.69 g,
25.5 mmol) and CCl4 (22.5 mL, 233 mmol) in CH2Cl2 (50 mL). After stirring over-
night (about 15 h), an additional portion of triphenylphosphine (1.83 g, 6.98 mmol)
was added, and the mixture was stirred for 4 h. The volatiles were removed, and
the residue was partitioned between ethyl acetate and water. The layers were sepa-
rated, and the aqueous phase was extracted using additional ethyl acetate. The com-
bined organic layer was washed with brine, dried, and concentrated. The residual oil
was dissolved in CH2Cl2:hexanes (1:1, 60 mL). The solution was scratched with a
glass rod until crystallization was induced. After setting for several hours, the pro-
duct 7 was filtered off using chilled CH2Cl2–hexanes (1:1) as a wash solvent. The fil-
trate was concentrated, and the resulting solid residue (mostly triphenylphosphine
oxide) was recrystallized from tert-butylmethylether. After filtering off the triphenyl-
phosphine oxide, the remaining filtrate was concentrated and then recrystallized
from CH2Cl2–hexanes (1:1) to obtain an additional crop of 7. The combined crops
afforded 4.21 g (14.5 mmol, 62%) of a white solid: mp 170–172.5 ꢁC; TLC, Rf ¼ 0.12,
ether; 1H NMR (DMSO-d6): 0.83 (t, J ¼ 7.2 Hz, 3H), 1.50 (m, 2H), 3.22 (t,
J ¼ 6.9 Hz, 2 H), 4.06 (s, 2H), 4.33 (s, 1H), 4.80 (s, 2H), 7.51 (m, 1H), 7.89 (m,
2H), 9.01 (s, 1H).
Reaction of Diorganozinc Reagents with Enaminone 7 to Produce 4
A mixture of 7 (1.0g, 3.45mmol) and ZnBr2 (0.16 g, 0.71mmol, dried under high
vacuum for 1 h at 180 ꢁC) was dissolved in CH2Cl2 (5.0 mL) under an argon atmos-
phere. The mixture was cooled in an ice bath and treated with the diorganozinc
reagent (10.35mmol, 3 equivalents), either neat or as a solution in CH2CI2. Following
the addition of the diorganozinc reagent, the mixture was warmed to ambient
temperature and stirred for 1 h. The mixture was then heated to reflux (bath tempera-
ture ꢀ45ꢁC) and stirred for 8–24h. The mixture was cooled to ambient temperature
and quenched by pouring slowly into excess cold aqueous NH4Cl. After stirring for
several minutes, ethyl acetate was added, and the layers separated. The aqueous phase
was extracted with additional ethyl acetate, and the combined organic layer washed