Methoxymethyl-triphenylphosphonium chloride → 5-Bromo-3-[2-methoxy-1-(2-methoxy-phenyl)-vinyl]-pyridin-2-ylamine

Temperature

0 °C

Into a 50 ml flame-dried round bottomed flask were added potassium bis(trimethylsilyl)amide (832 mg, 39.2 mmol) and anhydrous THF (10 ml). The slurry was cooled to 0° C. for 5 minutes under nitrogen, then (methoxymethyl)triphenylphosphonium chloride (1.53 g, 4.47 mmol) was added. The resulting red-orange solution was stirred at room temperature for 45 min, then a solution of (2-amino-5-bromo-pyridin-3-yl)-(2-methoxy-phenyl)-methanone (601 mg, 1.95 mmol in 10 ml THF) was added all at once. The reaction was stirred under nitrogen for 4 hours then quenched by addition of a saturated aqueous solution of ammonium chloride (25 ml). Ethyl acetate (100 ml) was added, and the layers were separated. The aqueous fraction was extracted three times with ethyl acetate, and the combined organic fractions were washed with brine, dried (Na2SO4), filtered and concentrated to give a brown, sticky oil. Purification by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes gave 554 mg (84%) of 5-bromo-3-[2-methoxy-1-(2-methoxy-phenyl)-vinyl]-pyridin-2-ylamine as a mixture of E- and Z-isomers.

1. customInto a 50 ml flame-dried round bottomed flask
2. stirringThe reaction was stirred under nitrogen for 4 hours
3. customthen quenched by addition of a saturated aqueous solution of ammonium chloride (25 ml)
4. additionEthyl acetate (100 ml) was added
5. customthe layers were separated
6. extractionThe aqueous fraction was extracted three times with ethyl acetate
7. washthe combined organic fractions were washed with brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated
11. customto give a brown, sticky oil
12. customPurification by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes

ORD record

ord-fc0c427d0a6a46eba0623918bf12f0c6

Source dataset

uspto-grants-2008_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07361763B2