Boron trifluoride etherate → 6-(5-Bromo-2-chlorobenzyl)-2,3-dihydrobenzo[b][1,4]dioxine

To a stirred suspension of 5-bromo-4-methoxy-2-chlorobenzoic acid (128, 4 g, 15.2 mmol) in dichloromethane (100 mL) was added oxalyl chloride (1.6 mL, 18.3 mmol) and DMF (2 drops) at 0° C. and stirred for 2 h. The mixture was concentrated, and the residual colorless solid was dissolved in dichloromethane (100 mL). To this solution were added 1,4-benzodioxane (2 mL, 16.7 mmol) and then AlCl3 (2.23 g, 16.7 mmol) portionwise. After being stirred at room temperature overnight, the mixture was poured into ice water and extracted with dichloromethane two times. The combined organic layers were washed with 1 M HCl, water, and brine, then dried over magnesium sulfate, filtered and concentrated in vacuo. The crude residue was diluted with dichloromethane/acetonitrile (35 mL/35 mL) and added triethylsilane (7.4 mL, 45.6 mmol) followed by boron trifluoride diethyl etherate (5.8 mL, 45.6 mmol) at −10° C. The solution was allowed to warm to room temperature over 5 h prior to quenching with saturated sodium bicarbonate solution. After removal of organic volatiles under a reduced pressure, the crude residue was purified by silica gel chromatography (3 to 10% tetrahydrofuran in hexane) to yield the title compound (130, 3.6 g, 9.74 mmol, 64%; 3 steps) as a white solid.

1. concentrationThe mixture was concentrated
2. dissolutionthe residual colorless solid was dissolved in dichloromethane (100 mL)
3. stirringAfter being stirred at room temperature overnight
4. extractionextracted with dichloromethane two times
5. washThe combined organic layers were washed with 1 M HCl, water, and brine
6. dry with materialdried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. additionThe crude residue was diluted with dichloromethane/acetonitrile (35 mL/35 mL)
10. customto quenching with saturated sodium bicarbonate solution
11. customAfter removal of organic volatiles under a reduced pressure
12. customthe crude residue was purified by silica gel chromatography (3 to 10% tetrahydrofuran in hexane)

ORDレコード

ord-c6ad84e679f648b2893019a5a921a183

出典データセット

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09371303B2