Ethyl cyanoacetate → cis-Cyano-[4-(octahydro-quinoline-1-carbonyl)-thiophen-2-yl]-acetic acid ethyl ester

HRID 1809108Notes

Reaction equation

[H-].[Na+].[CH2:3]([O:5][C:6](=[O:10])[CH2:7][C:8]#[N:9])[CH3:4].Br[C:12]1[S:16][CH:15]=[C:14]([C:17]([N:19]2[CH:28]3[CH:23]([CH2:24][CH2:25][CH2:26][CH2:27]3)[CH2:22][CH2:21][CH2:20]2)=[O:18])[CH:13]=1>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:3]([O:5][C:6](=[O:10])[CH:7]([C:8]#[N:9])[C:12]1[S:16][CH:15]=[C:14]([C:17]([N:19]2[C@@H:28]3[C@@H:23]([CH2:24][CH2:25][CH2:26][CH2:27]3)[CH2:22][CH2:21][CH2:20]2)=[O:18])[CH:13]=1)[CH3:4]

Participants

Conditions

Temperature: 60 °C

Procedure

Sodium hydride (60% dispersion in mineral oil; 400 mg) was added to a solution of ethylcyanoacetate (0.450 g) in THF (10 mL) and the mixture stirred for 10 minutes. A solution of (5-bromo-thiophen-3-yl)-(octahydro-quinolin-1-yl)-methanone (0.326 g) and PdCl2(PPh3)2 (0.035 g) in THF (2 mL) was then added dropwise and the mixture heated to 60° C. overnight. The solvent was evaporated and the residue purified by flash chromatography on silica, washing with cyclohexane and ethyl acetate. The fractions containing the desired product were concentrated under vacuum to give the title compound as a clear oil (0.198 g). LCMS m/z 361.27 [M+H]+ RT=3.80 min (Analytical Method 3).

Workup

customThe solvent was evaporated
customthe residue purified by flash chromatography on silica
washwashing with cyclohexane and ethyl acetate
additionThe fractions containing the desired product
concentrationwere concentrated under vacuum

Sources & evidence

ORD record: ord-62d9ceb81eeb411caac16488efe70c9d
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08362008B2

Reaction notes

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