3,4-DibroMo-2-(cyclopropylMethyl)thiophene synthesis

Yield:-

Reaction Conditions:

Stage #1:3,4-dibromothiophene with n-butyllithium;diisopropylamine in tetrahydrofuran at -78 - 0; for 0.5 h;
Stage #2:cyclopropylcarbinyl bromide at -78 - 20;

Steps:

1
Intermediate 13,4 -Dihromo-2-(ey lopropylmethyl)t.»ophe«eDi- -propy{avnine (637 itL, 4.55 mmol) was dissolved in THE ( i 5 ml) and cooled to °C. 1 eq. « -BuLi (4.55 mmol) was added and the mixture was stirred for 15 min. T his solution was added to 2,3- dibromoihiophene ( 1.0 g, 4.13 mmol) in TMF (8 ml) that was cooled to -78C. After 15 rain (b.romomethyi)cyelopropane (2.79 g, 20.7 mino.) was added and the mixture was allowed to warm io room temperature.. DCM and iM HCl were added and the phases were separated. After flashchromatographic separation 3_s4-dibronx>-2-(cyc]opropylmethyl}thiophene 640 nig, (2, 16 mmol) was obtained.Intermediate- 1 was used in the synthesis of Examples 10 and 11.

References:

KARO BIO AB;WU, Xiongyu;LÖFSTEDT, Joakim;KRÜGER, Lars;WENNERSTÅL, Mattias WO2012/22776, 2012, A1 Location in patent:Page/Page column 24-25