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In a typical experiment, THF (240 mL, dried over molecular sieves), 2,2,2-
trifluoroethanol[10] (19.2 g, 0.19 mol), and (1R,2S)-N-pyrrolidinylnorephedrine
(59.1 g, 0.29 mol) were mixed under nitrogen. The mixture was
cooled to 08C, and diethylzinc (1.1m in toluene, 218 mL, 0.24 mol) was
added slowly enough to keep the temperature below 308C. A solution of
chloromagnesium cyclopropylacetylide was prepared by reaction of cyclopropylacetylene
(15.9 g, 0.24 mol) and n-butylmagnesium chloride (2.0m in
THF, 120 mL, 0.24 mol) at 08C for 1 h. The solution was then transferred to
the zinc reagent by cannula with THF (100 mL) as a wash. The mixture was
cooled to 08C, and 1 (44.7 g, 0.20 mol) was added. The reaction mixture was
quenched with 1m citric acid (400 mL) after 15 h. The two layers were
separated. The aqueous layer was saved for recovery of (1R,2S)-Npyrrolidinylnorephedrine.
The organic layer (assay of this solution
indicated 99.2% ee[9]) was washed with water (200 mL) and concentrated
to about 180 mL. Toluene (100 mL) was added and the solution was again
concentrated to about 180 mL to remove all THF. Heptane (240 mL) was
added slowly. The mixture was cooled to 0 8C, and the solid was collected by
filtration, washed with heptane (ca. 50 mL), and dried to give 55.2 g (95.3%
yield, 99.2% ee) of analytically pure 4 as a white solid. M.p. 139 ± 1418C;
1H NMR (CDCl3 , 300 MHz): d7.52 (d, J2.4 Hz, 1 H), 7.12 (dd, J2.4,
8.7 Hz, 1H), 6.61 (d, J 8.7 Hz, 1H), 4.70 (s, 1H), 4.39 (s, 2H), 1.39 (m,
1H), 0.85 (m, 4H); 13C NMR (CDCl3 , 75.5 MHz): d143.21, 130.44,
130.04, 123.94, 123.93 (q), 121.11, 120.81, 93.51, 74.80 (q), 70.58, 8.59, ÿ0.85;
elemental analysis calcd for C13H11NOClF3 (%): C 53.80, H 3.77, N 4.72;
found: C 53.71, H 3.75, N 4.64.
