(S)-2-[2-(2-chloro-phenoxy)-3-propoxycarbonyl-allylamino]-4,4-difluoro-pentanoic acid methyl ester → HCID 66894484, compound

HRID 19310Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:28])[C@@H:4]([NH:10][CH2:11][C:12]([O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[Cl:27])=[CH:13][C:14](OCCC)=[O:15])[CH2:5][C:6]([F:9])([F:8])[CH3:7]>C(#N)C.ClCCl>[CH3:1][O:2][C:3](=[O:28])[C@@H:4]([N:10]1[CH2:11][C:12]([O:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[Cl:27])=[CH:13][C:14]1=[O:15])[CH2:5][C:6]([F:9])([F:8])[CH3:7]

Participants

Conditions

Temperature: 140 °C

Procedure

A solution of (S)-2-[2-(2-chloro-phenoxy)-3-propoxycarbonyl-allylamino]-4,4-difluoro-pentanoic acid methyl ester (255 mg, 0.63 mmol) in acetonitrile (2 mL) was placed in a sealed microwave reaction tube and heated in a microwave reactor at 140° C. for 3.5 h. The mixture was diluted with dichloromethane and concentrated in vacuo with silica gel (2 g). Purification by Biotage flash chromatography (Aspire 40 g column, 16% ethyl acetate/hexanes to 50% ethyl acetate/hexanes) afforded (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4,4-difluoro-pentanoic acid methyl ester (100 mg, 32% over two steps) as a colorless gum: HR-ES-MS m/z calculated for C16H16NO4ClF2 [M+Na]+ 382.0628, observed 382.0629.

Workup

concentrationconcentrated in vacuo with silica gel (2 g)
customPurification by Biotage flash chromatography (Aspire 40 g column, 16% ethyl acetate/hexanes to 50% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-88000f71ad5c4f61ad649f203f884576
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07741327B2

Reaction notes

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