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

HRID 1946557Notes

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-c84b30f45cc84e52a10b3171dae5dfa6
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399453B2

Reaction notes

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