Aluminium lithium hydride → HCID 66642809, compound

To a stirred suspension of LiAlH4 (0.26 g, 6.95 mmol) in THF (40 mL) at 0° C. was slowly added a solution of methyl 3,5-dichloro-4-[3′-(4-fluorobenzyl)-4′-methoxyphenoxy]benzoate (1.2 g, 2.76 mmol) in THF (10 mL). The reaction mixture was stirred at room temperature for 20 h and cooled to 0° C. The reaction mixture was quenched with 15% aqueous NaOH (1.5 mL), diluted with H2O (3.0 mL) and stirred for 1 h. The reaction mixture was filtered through a Celite plug and the filtrate was extracted with ethyl acetate (100 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel, eluting with ethyl acetate-hexanes (1:1) to afford 3,5-dichloro-4-[3′-(4-fluorobenzyl)-4′-methoxyphenoxy]benzyl alcohol as an oil (0.78 g, 70%): 1H NMR (300 MHz, CDCl3): δ 7.47 (s, 2H), 7.16 (dd, J=6.0, 8.7 Hz, 2H), 7.04 (t, J=8.7 Hz, 2H), 6.84 (d, J=9.0 Hz, 1H), 6.67 (d, J=3.0 Hz, 1H), 6.45 (dd, J=5.4, 9.3 Hz, 1H), 5.45 (t, J=5.7 Hz, 1H), 4.48 (d, J=5.7 Hz, 2H), 3.82 (s, 2H), 3.69 (s, 3H); TLC conditions: Uniplate silica gel, 250 microns; Mobile phase=ethyl acetate-hexanes (2:3); Rf=0.45.

1. temperaturecooled to 0° C
2. customThe reaction mixture was quenched with 15% aqueous NaOH (1.5 mL)
3. additiondiluted with H2O (3.0 mL)
4. stirringstirred for 1 h
5. filtrationThe reaction mixture was filtered through a Celite plug
6. extractionthe filtrate was extracted with ethyl acetate (100 mL)
7. washThe combined organic layers were washed with brine
8. dry with materialdried over Na2SO4
9. concentrationconcentrated under reduced pressure
10. customThe crude product was purified by column chromatography on silica gel
11. washeluting with ethyl acetate-hexanes (1:1)

ORD record

ord-f9a19a8fefa44c529bec651ff23ef1b6

Source dataset

uspto-grants-2009_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07514419B2