Triethylamine → (2R)-3-bromo-N-(3-chloro-4-cyanophenyl)-2-hydroxy-2-methylpropanamide

Thionyl chloride (7.8 g, 65.5 mmol) was added dropwise to a cooled solution (less than 4° C.) of (R)-3-bromo-2-hydroxy-2-methylpropanoic acid (9.0 g, 49.2 mol) in 50 mL of THF under an argon atmosphere. The resulting mixture was stirred for 3 h under the same condition. To this was added Et3N (6.6 g, 65.5 mol) and stirred for 20 min under the same condition. After 20 min, 4-amino-2-chlorobenzonitrile (5.0 g, 32.8 mmol) and 100 mL of THF were added and then the mixture was allowed to stir overnight at room temperature. The solvent was removed under reduced pressure to give a solid which was treated with 100 mL of H2O, extracted with EtOAc (2×150 mL). The combined organic extracts were washed with saturated NaHCO3 solution (2×100 mL) and brine (300 mL), successively. The organic layer was dried over MgSO4 and concentrated under reduced pressure to give a solid which was purified from column chromatography using EtOAc/hexane (50:50) to give 7.7 g (49.4%) of target compound as a brown solid.

1. stirringstirred for 20 min under the same condition
2. waitAfter 20 min
3. stirringto stir overnight at room temperature
4. customThe solvent was removed under reduced pressure
5. customto give a solid which
6. extractionextracted with EtOAc (2×150 mL)
7. washThe combined organic extracts were washed with saturated NaHCO3 solution (2×100 mL) and brine (300 mL)
8. dry with materialThe organic layer was dried over MgSO4
9. concentrationconcentrated under reduced pressure
10. customto give a solid which
11. customwas purified from column chromatography
12. customto give 7.7 g (49.4%) of target compound as a brown solid

ORD record

ord-9f004cb4c673495f895925e854404709

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08669286B2