2-[2-(2-Chloro-phenoxy)-3-ethoxycarbonyl-allylamino]-5,5,5-trifluoro-4-trifluoromethyl-pentanoic acid methyl ester → 2-[4-(2-Chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5,5-trifluoro-4-trifluoromethyl-pentanoic acid methyl ester

HRID 19314Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:32])[CH:4]([NH:15][CH2:16][C:17]([O:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[Cl:31])=[CH:18][C:19]([O:21]CC)=O)[CH2:5][CH:6]([C:11]([F:14])([F:13])[F:12])[C:7]([F:10])([F:9])[F:8]>C(#N)C>[CH3:1][O:2][C:3](=[O:32])[CH:4]([N:15]1[CH2:16][C:17]([O:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[Cl:31])=[CH:18][C:19]1=[O:21])[CH2:5][CH:6]([C:11]([F:12])([F:13])[F:14])[C:7]([F:10])([F:9])[F:8]

Participants

Conditions

Temperature: 180 °C

Procedure

A solution of 2-[2-(2-chloro-phenoxy)-3-ethoxycarbonyl-allylamino]-5,5,5-trifluoro-4-trifluoromethyl-pentanoic acid methyl ester (144 mg, 0.29 mmol) in acetonitrile (2 mL) was placed in a sealed microwave reaction tube and heated in a microwave reactor at 180° C. for 3 h. The mixture was cooled to room temperature and concentrated in vacuo with silica gel (1.2 g). Purification by Biotage flash chromatography (AnaLogix 25 g column, 16% ethyl acetate/hexanes to 33% ethyl acetate/hexanes) afforded 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5,5-trifluoro-4-trifluoromethyl-pentanoic acid methyl ester (52 mg, 7% over two steps) as an amber oil: HR-ES-MS m/z calculated for C17H14NO4ClF6 [M+H]+ 446.0589, observed 446.0588.

Workup

temperatureThe mixture was cooled to room temperature
concentrationconcentrated in vacuo with silica gel (1.2 g)
customPurification by Biotage flash chromatography (AnaLogix 25 g column, 16% ethyl acetate/hexanes to 33% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-361656979e4a489c83f7685d56e5ed74
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07741327B2

Reaction notes

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