Trifluoroacetic acid → HCID 22144484, compound

Temperature

2.5 °C

Under a nitrogen atmosphere, a cold (0-5° C.), stirring solution of (4E)-N-methyl-N-(tert-butoxycarbonyl)-5-(6-methoxy-3-pyridyl)-4-penten-2-amine (2.90 g, 9.45 mmol) in dichloromethane (20 mL) was treated drop-wise over 15 min with trifluoroacetic acid (15 mL). After stirring for 30 min, the solution was concentrated to a yellow-orange oil. The residue was diluted with saturated aqueous NaCl solution (15 mL), cooled to 0-5° C., and basified with 10% aqueous NaOH solution (22 mL). The mixture was extracted with CHCl3 (5×25 mL). The combined CHCl3 extracts were dried (Na2SO4), filtered, and concentrated under vacuum to give a light-yellow oil (1.88 g). The crude product was purified by column chromatography on silica gel (70-230 mesh) (150 g), eluting with a CH3OH—NH4OH step-wise gradient (100:1→15:1 in increments of 25:1). Fractions containing the product (Rf 0.28 in CHCl3—CH3OH-Et3N (50:1:1)) were kept separate from those containing an impurity (Rf 0.35) and were combined and concentrated to give 0.76 g of a light-yellow oil. Impure fractions were combined and concentrated to give 1.20 g of light-yellow oil. The latter material was re-chromatographed on a new silica gel column (75 g) using the same CH3OH—NH4OH gradient elution protocol. Impure fractions were combined and concentrated to give 1.08 g of light-yellow oil. The latter material was re-chromatographed (6 times) on a new silica gel columns (45 g and 25 g) using CHCl3—CH3OH-Et3N step-wise gradient (16:1→1:1 in CHCl3—CH3OH, with each gradient step containing 1% Et3N). All fractions containing the product were combined and concentrated under vacuum to give 1.368 g (70.2%) of a light-yellow oil.

1. concentrationthe solution was concentrated to a yellow-orange oil
2. additionThe residue was diluted with saturated aqueous NaCl solution (15 mL)
3. extractionThe mixture was extracted with CHCl3 (5×25 mL)
4. dry with materialThe combined CHCl3 extracts were dried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated under vacuum

ORD record

ord-4c53aaa6536c4a04bb8577420f615efb

Source dataset

uspto-grants-2005_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06979695B2