Hydrochloric Acid → (R)-2-(3,4-Dichloro-phenylamino)-propionic acid

HRID 2095503

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4](I)[CH:5]=[CH:6][C:7]=1[Cl:8].[NH2:10][C@@H:11]([C:13]([OH:15])=[O:14])[CH3:12].C1(NN=CC2C=CC=CC=2O)C=CC=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl>CN(C)C=O.O.[Cu]I>[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C@H:11]([CH3:12])[C:13]([OH:15])=[O:14])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 6.00 g (22.00 mmol) 3,4-dichloroiodobenzene, 2.94 g (33.00 mmol) D-alanine, 0.42 g (2.20 mmol) copper(I) iodide, 0.96 g (4.40 mmol) 2-hydroxybenzaldehyde phenylhydrazone, 14.00 g (66.00 mmol) tri-potassium phosphate in 32 ml of N,N-dimethylformamide was stirred at 80° C. for 16 h under argon, then after cooling diluted with water and acidified to pH 3 by addition of 25% aq. HCl solution. The mixture was extracted with EtOAc (3×), the organic phases were washed with brine, dried (Na2SO4), filtered and evaporated. Flash chromatography (SiO2; dichloromethane/MeOH 95:5 to 4:1) afforded 3.11 g (60%) of the title compound (as 81:19 mixture of the (R) and (S) stereoisomers, BGB-175*0.25 column) as light brown solid. MS: 231.9 (M−H−, 2Cl).

Workup

temperatureafter cooling
extractionThe mixture was extracted with EtOAc (3×)
washthe organic phases were washed with brine
dry with materialdried (Na2SO4)
filtrationfiltered
customevaporated

Sources & evidence

ORD record: ord-762c2d4777384a30afd91c16ba20d130
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08445674B2

Linked notes

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