Borane;tetrahydrofuran → HCID 66724839, compound

Temperature

0 °C

Two-hundred (200) mg (0.48 mmol) of Boc-(3R)-4-amino-3-[4-chloro-3-(3-cyanophenyl)phenyl]butanoic acid (52a) (200 mg, 0.48 mmol) was dissolved in 1 mL of tetrahydrofuran (THF). The reaction mixture was cooled to 0° C. and 3 equivalents of 2M borane/THF solution was added. The mixture was warmed to room temperature and stirred for 3 days. The reaction mixture was then carefully quenched with excess methanol. After stirring for 15 min, 2 mL of 1N NaOH was added and the mixture stirred for one hour. The mixture was extracted with ethyl acetate (3×10 mL), the aqueous solution acidified to pH 3, and then extracted two additional times with ethyl acetate. The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude residue was purified by HPLC to provide the title compound (53) (4.3 mg, 10% yield). 1H-NMR (400 MHz, CD3OD): δ 1.93-2.01 (m, 1H), 1.81-1.88 (m, 1H), 3.22-3.27 (dd, J=22.4, 9.6 Hz, 1H), 3.14-3.19 (m, 1H), 3.30-3.39 (m, 1H), 3.52-3.57 (m, 1H), 7.54-7.56 (m, 1H), 7.33-7.36 (m, 2H), 7.61-7.65 (m, 1H), 7.75-7.78 (m, 1H), 7.80-7.81 (m, 1H); MS (ESI) m/z 301.04 (M+H)+.

1. temperatureThe mixture was warmed to room temperature
2. customThe reaction mixture was then carefully quenched with excess methanol
3. stirringAfter stirring for 15 min
4. addition2 mL of 1N NaOH was added
5. stirringthe mixture stirred for one hour
6. extractionThe mixture was extracted with ethyl acetate (3×10 mL)
7. extractionextracted two additional times with ethyl acetate
8. dry with materialThe combined organic layers were dried over Na2SO4
9. concentrationconcentrated in vacuo
10. customThe crude residue was purified by HPLC

ORD record

ord-d5c8c8cf0e964b229b0f64b44acca200

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08344028B2