Water → Diethyl ((2-bromo-4-methylphenyl)difluoromethyl)phosphonate

A solution of (bromo-difluoro-methyl)-phosphonic acid diethyl ester (25.00 g, 93.6 mmol) in N,N-dimethylacetamide (50 mL) was added drop wise into a suspension of activated zinc (6.12 g, 93.6 mmol) under Argon. The reaction was initiated by heating and kept under 50° C. After the mixture was stirred for 3 h, copper (I) bromide (13.43 g, 93.6 mmol) was added and stirred for 1 h. A solution of 2-bromo-1-iodo-4-methyl-benzene (11.88 g, 40.0 mmol) in N,N-dimethylacetamide (25 mL) was added slowly to the reaction mixture. The resulting suspension was then stirred at room temp for 18 h. Water (100 mL) was added to the reaction mixture and the solution filtered through celite. The filtrate was diluted with EtOAc (250 mL) and organic layer was washed with H2O (50 mL), NaHCO3 (5%, 50 mL) and H2O (50 mL). The solvent was removed and the residue was purified by column chromatography on silica gel, eluting with hexanes/EtOAc (4:1) to provide a colorless oil (11.75 g, 82%): 1H NMR (300 MHz, CDCl3) δ 7.51 (d, 1H), 7.49 (s, 1H), 7.19 (d, 1H), 4.26 (m, 4H), 2.36 (s, 3H), 1.48 (s, 9H), 137 (m, 6 H).

1. temperatureby heating
2. customkept under 50° C
3. stirringstirred for 1 h
4. stirringThe resulting suspension was then stirred at room temp for 18 h
5. filtrationthe solution filtered through celite
6. additionThe filtrate was diluted with EtOAc (250 mL) and organic layer
7. washwas washed with H2O (50 mL), NaHCO3 (5%, 50 mL) and H2O (50 mL)
8. customThe solvent was removed
9. customthe residue was purified by column chromatography on silica gel
10. washeluting with hexanes/EtOAc (4:1)

ORD 기록

ord-ff395510623945659e3a678161892b75

출처 데이터셋

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07381736B2