Potassium Hydroxide → 5-Bromo-2-(difluoromethoxy)-1,3-dimethoxybenzene

温度

-78 °C

5-Bromo-2-(difluoromethoxy)-1,3-dimethoxybenzene was synthesized from 4-bromo-2,6-dimethoxyphenol according to the procedure of Zafrani, Y. Tetrahedron 2009, 65, 5278 as follows. To a solution of 4-bromo-2,6-dimethoxyphenol (1.08 g, 4.6 mmol) in MeCN (27 mL) was added a solution of KOH (5.0 g, 89 mmol) in H2O (27 mL). The mixture was immediately cooled over a −78° C. bath and diethyl(bromodifluoromethyl)phosphonate (1.6 mL, 8.9 mmol) was added. The flask was sealed with a septum and the cold bath was removed. The mixture was stirred for a total of 3.5 hrs during which time the septum was ejected from the flask. The reaction was diluted with EtOAc and the layers were separated. The aqueous layer was extracted with EtOAc and the combined organics were washed with 1 M NaOH, H2O and brine then dried over Na2SO4 and concentrated in vacuo. Purification by chromatography (0-30% EtOAc-hexanes) provided 5-bromo-2-(difluoromethoxy)-1,3-dimethoxybenzene as a white solid (0.808 g, 62% yield).

1. customThe flask was sealed with a septum
2. customthe cold bath was removed
3. additionThe reaction was diluted with EtOAc
4. customthe layers were separated
5. extractionThe aqueous layer was extracted with EtOAc
6. washthe combined organics were washed with 1 M NaOH, H2O and brine
7. dry with materialthen dried over Na2SO4
8. concentrationconcentrated in vacuo
9. customPurification by chromatography (0-30% EtOAc-hexanes)

ORDレコード

ord-11df3402760d45b2a0c38bdeab5e3b2c

出典データセット

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09434707B2