Acetonitrile → HCID 178500465, compound

HRID 19305Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:12])[CH:4]([NH2:11])[CH2:5][C@H:6]1[CH2:9][C@@H:8]([CH3:10])[CH2:7]1.C(#N)C.C(N(CC)C(C)C)(C)C.[Cl:25][C:26]1[CH:59]=[CH:58][CH:57]=[CH:56][C:27]=1[O:28][C:29]1[CH2:33]N([C@@H](CC2CCCCC2)C(NC2C=CN(CC(O)(C)C)N=2)=O)[C:31](=[O:55])[CH:30]=1>ClCCl>[CH3:1][O:2][C:3](=[O:12])[CH:4]([N:11]1[CH2:33][C:29]([O:28][C:27]2[CH:56]=[CH:57][CH:58]=[CH:59][C:26]=2[Cl:25])=[CH:30][C:31]1=[O:55])[CH2:5][C@H:6]1[CH2:7][C@@H:8]([CH3:10])[CH2:9]1

Participants

Conditions

Temperature: 80 °C

Procedure

In a small pressure bottle was placed a mixture 2-amino-3-(cis-3-methyl-cyclobutyl)-propionic acid methyl ester (133 mg, 0.78 mmol), acetonitrile (10 mL) and N,N-diisopropylethylamine (200 μL, 0.94 mmol) and the resulting mixture heated to 80° C. To this mixture was added (E)-4-bromo-3-(2-chloro-phenoxy)-but-2-enoic acid ethyl ester (prepared as in Example 61, 250 mg, 0.78 mmol) in dichloromethane (5 mL) and the tube sealed and heated at 100° C. overnight. The mixture was then cooled and concentrated in vacuo with silica gel (2 g). Purification by Biotage flash chromatography (40S column, 20% ethyl acetate/hexanes to 40% ethyl acetate/hexanes) afforded 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-(cis-3-methyl-cyclobutyl)-propionic acid methyl ester (103 mg, 36%) as an amber gum: HR-ES-MS m/z calculated for C19H22NO4Cl [M+Na]+ 386.1129, observed 386.1130.

Workup

customthe tube sealed
temperatureheated at 100° C. overnight
temperatureThe mixture was then cooled
concentrationconcentrated in vacuo with silica gel (2 g)
customPurification by Biotage flash chromatography (40S column, 20% ethyl acetate/hexanes to 40% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-1475076d6831459880181a351a455f86
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07741327B2

Reaction notes

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