Tert-butoxycarbonylalanine → HCID 178496640, compound

Temperature

0 °C

A mixture of 4-fluoro-N2-(cis-3-methoxycyclobutyl)benzene-1,2-diamine (0.34 g, 1.6 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (0.33 g, 1.8 mmol) and HOAt (0.24 g, 1.8 mmol) in DCM (8 mL) was cooled to 0° C. under a nitrogen atmosphere. To this mixture was added N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (0.35 g, 1.8 mmol) portion wise and the mixture stirred at RT for 1 h. The reaction mixture allowed to warm to RT then partitioned between DCM (30 mL) and saturated aqueous solution of NaHCO3 (20 mL). The organic fraction was washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane) to afford the compound as a pink oil (0.348 g, 57%). The compound thus obtained was dissolved in AcOH (8 mL) and heated at 70° C. for 18 h. After cooling to RT, the volatiles were evaporated in vacuo and the residue partitioned between DCM (40 mL) and a saturated aqueous solution of NaHCO3 (20 mL). The organic fraction was washed with brine (20 mL), dried (MgSO4) then concentrated in vacuo. The resulting dark brown residue was purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane) to afford the title compound as yellow oil (0.222 g, 38%). LCMS (Method B): RT 2.86 min [M+H]+ 364.03

1. temperatureto warm to RT
2. customthen partitioned between DCM (30 mL) and saturated aqueous solution of NaHCO3 (20 mL)
3. washThe organic fraction was washed with brine (20 mL)
4. dry with materialdried (MgSO4)
5. concentrationconcentrated in vacuo
6. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane)

ORD record

ord-b679ee37677e4f05a30e951e99574284

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653089B2