1,3-Dibromopropane → Methyl 5-bromo-2-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pentanoate

Temperature

0 °C

Sodium hydride (0.153 g, 3.83 mmol) was added in one portion to methyl 2-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetate (Intermediate 2-7; 1.08 g, 3.48 mmol) in DMF (20 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes. 1,3-Dibromopropane (0.392 mL, 3.83 mmol) was added to the reaction and was stirred at 0° C. for 5 minutes. Sodium hydride (0.153 g, 3.83 mmol) was added in one portion to the reaction and stir at 0° C. for 1 hour. The reaction mixture was quenched with saturated NH4Cl (50 mL). The reaction mixture was diluted with EtOAc (75 mL), and washed sequentially with water (4×50 mL) and saturated brine (50 mL). dried over MgSO4 The organic layer was evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford methyl 5-bromo-2-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pentanoate (0.362 g, 24.12%) as a colourless gum.

1. stirringwas stirred at 0° C. for 5 minutes
2. stirringstir at 0° C. for 1 hour
3. customThe reaction mixture was quenched with saturated NH4Cl (50 mL)
4. additionThe reaction mixture was diluted with EtOAc (75 mL)
5. washwashed sequentially with water (4×50 mL) and saturated brine (50 mL)
6. dry with materialdried over MgSO4 The organic layer
7. customwas evaporated
8. customto afford crude product
9. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane
10. customPure fractions were evaporated to dryness

ORD record

ord-b7fc5e39f6714b74ba8f022db7bf3fbe

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08188092B2