Malonate Ion → 2-{2-Chloro-4-[2-(2-cyclopentyl-4,6-dioxo-tetrahydro-pyran-2-yl)-ethyl]-phenyl}-2-methyl-propionitrile

HRID 1438369Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][C:15]([CH:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)([OH:20])[CH2:16][C:17](O)=[O:18])[CH:5]=[CH:6][C:7]=1[C:8]([C:11]#[N:12])([CH3:10])[CH3:9].C1N=CN(C(N2C=NC=C2)=O)C=1.C([O-])(=O)[CH2:39][C:40]([O-])=[O:41]>C(C(C(OC(C)(C)C)=O)C(OC)=O)C.CN(C1C=CN=CC=1)C.C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:13][CH2:14][C:15]2([CH:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)[CH2:16][C:17](=[O:18])[CH2:39][C:40](=[O:41])[O:20]2)[CH:5]=[CH:6][C:7]=1[C:8]([CH3:10])([CH3:9])[C:11]#[N:12]

Participants

Conditions

Temperature: 42 °C

Procedure

5-[3-Chloro-4-(cyano-dimethyl-methyl)-phenyl]-3-cyclopentyl-3-hydroxy-pent-4-enoic acid, from step 1 above, was dissolved in methyl tert-butyl ethylmalonate (3 mL). 4-DMAP (0.16 g, 0.13 mmol) and CDI (0.27 g, 1.68 mmol) were added and the reaction mixture was stirred under argon for 2 hours. In a separate flask was placed magnesium-bis-monoethyl malonate (0.74 g, 2.58 mmol) was suspended in THF (3 mL) and the mixture was heated to 42° C. The acylimidazole solution was added via cannula to the malonate mixture and the reaction was heated to 42° C. for 2 hours. The solvent was removed in vacuo to give a residue that was partitioned between 1 N HCl and EtOAc. The organic layer was dried over MgSO4 and concentrated to a clear oil (0.56 g, 100%).

Workup

customIn a separate flask was placed
temperaturethe reaction was heated to 42° C. for 2 hours
customThe solvent was removed in vacuo
customto give a residue that
customwas partitioned between 1 N HCl and EtOAc
dry with materialThe organic layer was dried over MgSO4
concentrationconcentrated to a clear oil (0.56 g, 100%)

Sources & evidence

ORD record: ord-208f0f4d021740f090899c28169429db
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07622605B2

Reaction notes

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