Benzyl iodide → Thiophene, 2-(phenylmethyl)-

A solution of 7.8 g (52 mmol) of NaI and 5 mL (43 mmol) of benzyl chloride in THF was heated at reflux for 2 h to form benzyl iodide in situ and then the reaction was cooled to rt. In a separate flask, 37 mg (0.87 mmol) of LiCl and 58 mg (0.43 mmol) of copper(II) chloride were dissolved in 5 mL of THF and stirred at rt for 5 min to form Li2CuCl4 in situ. The benzyl iodide reaction flask was fitted with an addition funnel and 3 mL (3 mmol) of a 1 M solution of 2-thienylmagnesium bromide in THF was added dropwise, followed by addition of the Li2CuCl4 solution, and then the remaining 2-thienylmagnesium bromide solution (49 mL, 49 mmol) was added at such a rate as to maintain the reaction temperature <40° C. and the reaction solution was stirred for 2 h at rt. The THF was removed in vacuo, and the residue was partitioned between 250 mL of Et2O and 150 mL of NH4Cl and separated. The organic layer was treated with 15 mL of piperidine and stirred for 18 h, then washed twice with 10% (w/v) aqueous HCl, filtered, concentrated and the dark red residue was purified by flash chromatography eluting with neat hexane to yield the title compound. GC-MS (M)+ 174.

1. customwas fitted with an addition funnel
2. temperatureto maintain the reaction temperature <40° C.
3. customThe THF was removed in vacuo
4. customthe residue was partitioned between 250 mL of Et2O and 150 mL of NH4Cl
5. customseparated
6. additionThe organic layer was treated with 15 mL of piperidine
7. stirringstirred for 18 h
8. washwashed twice with 10% (w/v) aqueous HCl
9. filtrationfiltered
10. concentrationconcentrated
11. customthe dark red residue was purified by flash chromatography
12. washeluting with neat hexane

ORD record

ord-feade622c5d74648b49dfbe17d12f69c

Source dataset

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07786132B2