3-n-Octyl-2-(4,4,5,5-tetraMethyl-1,3,2-dioxaborolan-2-yl)thiophene synthesis

Yield:405165-14-2 64%

Reaction Conditions:

Stage #1: 2-bromo-3-octylthiophenewith n-butyllithium in tetrahydrofuran;hexane at -78; for 2.25 h;Inert atmosphere;
Stage #2: 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in tetrahydrofuran;hexane at -78 - 25; for 17 h;

Steps:

1 Synthesis of 4,4,5,5-tetramethyl-2-(3-octylthiophen-2-yl)-1 ,3,2-dioxaborolane having formula (2)

Synthesis of 4,4,5,5-tetramethyl-2-(3-octylthiophen-2-yl)-1 ,3,2-dioxaborolane having formula (2) (0144) In a 250 ml three-neck flask equipped with a dropping funnel, an inert atmosphere was created through nitrogen (N₂) insufflation. Subsequently, 5.0 g (18.16 mmol) of 2-bromo- 3-octylthiophene having formula (1) and 90 ml of tetrahydrofuran (THF) anhydrous were added. The solution obtained was cooled to -78°C and 8.0 ml of n-butyl-lithium (LiBu) (2.5 M in hexane) were added slowly, over 15 minutes. The reaction mixture obtained was kept, under stirring, at -78°C, for a further 2 hours, at the end of which 6.76 g (36.32 mmol) of 2-i^'so-propoxy-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane were added, and subsequently heated, under stirring, slowly, over 1 hour, to ambient temperature (25°C). After 16 hours, under stirring, at ambient temperature (25°C), the reaction was stopped by adding 1 10 ml of a saturated aqueous solution of sodium bicarbonate (NaHC0₃) and the residual solvent was removed through distillation at reduced pressure. The residue obtained having pH ~ 1 1 , was brought to pH 8 through the addition of 13 ml of a 10% hydrochloric acid (HCI) solution, and then extracted with ethyl acetate (3 x 150 ml). The global organic phase (obtained by joining the three organic phases obtained from the extraction) was washed with a saturated aqueous solution of sodium chloride (NaCI) (3 x 100 ml) and subsequently anhydrified on sodium sulfate anhydrous for 3 hours. The residual solvent was then removed through distillation at reduced pressure, obtaining a dark yellow oil, which was dissolved in 100 ml of ethyl acetate and filtered on Celite 545: the residual solvent was removed again at reduced pressure obtaining a light yellow oil. Said light yellow oil was purified through chromatography on a silica gel column using a hexane/ethyl ether mixture (39/1 v/v) as eluent obtaining 3.68 g (yield 64%) of 4,4,5,5- tetramethyl-2-(3-octylthiophen-2-yl)-1 ,3,2-dioxaborolane having formula (2), as a colorless oil, which was characterized through ¹ H-NMR (400 MHz, CDCI₃) obtaining the following spectrum: δ 7.48 (d, J≈ 5 Hz, 1 H), 7.01 (d, J≈ 5 Hz, 1 H), 2.88 (t, J= 7.5 Hz, 2H), 1.65-1.10 (m, 24H), 0,88 (t, J= 7.5 Hz, 3H) ppm; and through ¹³C-NMR (100 MHz, CDCI₃) obtaining the following spectrum: δ 154.7, 131.2, 130.3, 83.5, 31.9, 31.8, 30.1 , 29.4, 29.3 (double signal), 24.8, 22.7, 14.1 ppm.

References:

WO2017/199151,2017,A1 Location in patent:Page/Page column 26-28