(2-IODOETHYL) CYCLOPROPANE synthesis

Yield: 62%

Reaction Conditions:

with 1H-imidazole;iodine;triphenylphosphine in dichloromethane at 0 - 30;

Steps:

15.A Part A.
2-Cyclopropylethanol, (21.35 g, 248 mmol, Lancaster), imidazole (25.32 g, 372.4 mmol, Aldrich), and [TRIPHENYLPHOSPHINE] (84.64 g, 323 mmol, Aldrich) were dissolved into methylene chloride (300 mL). The resulting mixture was cooled to [0°C] in an ice bath. Afterward, iodine (75.37 g, 298 mmol, Aldrich) was added portion- wise such that the temperature remained at less than [30°C.] After this addition was complete, the mixture was allowed to warm to ambient temperature and mix under N2 overnight. The mixture was then diluted with deionized water (250 mL). Subsequently, the layers were separated. The methylene chloride layer was washed with 200 mL each of 10% HCl (aq) (200 mL), saturated [NAHC03 (AQ)] (200 mL), and 10g Na2S203 in deionized water (200 mL). The methylene chloride layer was dried over [MGS04,] filtered, and concentrated in vacuo with a rotovap having a bath temperature of less than [25°C] to form solids. Hexanes (150 mL) were added to the solids, and the mixture was slurried for approximately [LHR.] The solids were-then filtered and washed with hexanes (150 mL). The filtrate was passed through a pad of silica (pre-washed with hexanes), with the silica being washed with hexanes to elute the product through the silica. Five bulk fractions of 350 mL each were taken. Product was detected in the first 3 fractions, and had little [TRIPHENYLPHOSPHINE] contamination. Those fractions were combined and concentrated in vacuo with a [ROTOTRAP] having a bath temperature of less than [25°C] to form 30.08 g of an oil (62% [YIELD). 1H] NMR was consistent with the desired cyclopropyl ethyl iodide intermediate product.

References:

PHARMACIA CORPORATION WO2004/811, 2003, A1 Location in patent:Page 170-171