2-(3,4-Dichloro-phenylamino)-propionic Acid → 2-(3,4-Dichloro-phenylamino)-propan-1-ol

33.11 ml (33.11 mmol, 1 M in THF) of a borane-tetrahydrofuran complex solution was added dropwise at 0° C. to a solution of 3.10 g (13.24 mmol) 2-(3,4-dichloro-phenylamino)-propionic acid (synthesized in analogy to intermediate 11, with 3,4-dichloroiodobenzene, D-alanine and copper(I) iodide, 2-hydroxybenzaldehyde phenylhydrazone and tri-potassium phosphate in N,N-dimethylformamide; enantiomeric ratio 71:29) in 50 ml THF, then after 10 min the ice bath was removed and the solution stirred for 2 h at RT. After cooling, 22 ml of MeOH and 1.1 ml of H2SO4 were added, and after 30 min at RT and 1 h at reflux the reaction mixture was concentrated in vacuo. The residue was partitioned between NaCl sat. 1 M aq. sodium hydroxide solution and EtOAc (3×). The organic layer was washed with brine, dried (Na2SO4), filtered, and evaporated. Flash silica gel column (CH2Cl2/MeOH 99:1→98:2) afforded 2.90 g (99%) of the title compound as a 71:29 mixture of the (R) and (S) stereoisomers. Yellow oil, MS: 220.0 (MH+, 2Cl)

1. customafter 10 min the ice bath was removed
2. temperatureAfter cooling
3. addition22 ml of MeOH and 1.1 ml of H2SO4 were added
4. waitafter 30 min at RT
5. temperature1 h at reflux the reaction mixture
6. concentrationwas concentrated in vacuo
7. customThe residue was partitioned between NaCl sat. 1 M aq. sodium hydroxide solution and EtOAc (3×)
8. washThe organic layer was washed with brine
9. dry with materialdried (Na2SO4)
10. filtrationfiltered
11. customevaporated

ORD record

ord-7ea54cb6ffbb4f729e7224af5892e356

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08138175B2