L-Serine → 2-acetamido-3-(6-chloro-5-fluoro-1H-indol-3-yl)propanoic acid

HRID 555339Notes

Reaction equation

[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][C:3]=1[F:11].[CH3:12][C:13](OC(C)=O)=[O:14].[NH2:19][C@H:20]([C:23]([OH:25])=[O:24])[CH2:21]O>CC(O)=O>[C:13]([NH:19][CH:20]([CH2:21][C:6]1[C:5]2[C:9](=[CH:10][C:2]([Cl:1])=[C:3]([F:11])[CH:4]=2)[NH:8][CH:7]=1)[C:23]([OH:25])=[O:24])(=[O:14])[CH3:12]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 6-chloro-5-fluoroindole (1.8 g, 10.8 mmol) and Ac2O (10 mL) in AcOH (30 mL) was added L-serine (2.2 g, 20.9 mmol), the mixture was heated to 80° C. After TLC indicated the reaction was complete, the mixture was cooled to 0° C., neutralized to pH 11, and washed with MTBE. The aqueous phase was acidified to pH 2 and extracted with EtOAc. The combined organic layers were washed with water and brine, dried with Na2SO4, filtered, and concentrated. The residue was purified with chromatography (Petroleum ether/EtOAc 1:1) to give 2-acetylamino-3-(6-chloro-5-fluoro-1H-indol-3-yl)-proprionic acid as a light yellow solid (1.2 g, 37% yield).

Workup

temperaturethe mixture was cooled to 0° C.
washwashed with MTBE
extractionextracted with EtOAc
washThe combined organic layers were washed with water and brine
dry with materialdried with Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified with chromatography (Petroleum ether/EtOAc 1:1)

Sources & evidence

ORD record: ord-dd62cebfdb2a4dbe8bf5ac666e609094
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08053442B2

Reaction notes

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