Chlorotrimethylsilane → Ethyl 2-(4-chloro-1-hydroxy-6-(tetrahydro-2H-pyran-2-yloxy)-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetate

Temperature

55 °C

To a suspension of powdered zinc dust (1.0 g, 2.73 mmol) in THF (3 mL) was added trimethylsilyl chloride (0.21 mL, 2.73 mmol) at 40° C. The mixture was stirred at 55° C. for 15 min. After cooled to 37° C., ethyl bromoacetate (1.21 mL, 13.65 mmol) was added slowly while maintaining the temperature between 37˜40° C. The resulting mixture was stirred at ambient temperature for an additional 30 min. To a solution of 2-chloro-4-(tetrahydro-2H-pyran-2-yloxy)-6-(4,4,5,5-tetramethyl-1,3,2-dioxa-borolan-2-yl)benzaldehyde (1 g, 2.73 mmol) in anhydrous THF (3 mL) cooled at −78° C., was added above freshly prepared zinc reagent. Upon completion of addition, the reaction mixture was warmed to room temperature and stirred for 30 min before quenched with saturated aqueous NH4Cl. The resulting mixture was extracted with EtOAc (2×30 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was used directly in the next step reaction without further purification. MS (ESI) m/z=355 [M+H]+.

1. temperatureAfter cooled to 37° C.
2. temperaturewhile maintaining the temperature between 37˜40° C
3. stirringThe resulting mixture was stirred at ambient temperature for an additional 30 min
4. additionUpon completion of addition
5. temperaturethe reaction mixture was warmed to room temperature
6. stirringstirred for 30 min
7. custombefore quenched with saturated aqueous NH4Cl
8. extractionThe resulting mixture was extracted with EtOAc (2×30 mL)
9. washThe combined organic layers were washed with brine (20 mL)
10. dry with materialdried over anhydrous Na2SO4
11. concentrationconcentrated in vacuo
12. customThe crude product was used directly in the next step reaction without further purification

ORD record

ord-8044aa0e11504f68a808d2bb6eda9352

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08343944B2