Tetrahydrofuran → Ethyl 2-(2-(tert-butoxycarbonylamino)pyridin-4-yl)propanoate

HRID 2069058Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([CH:8]([CH3:14])[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:5]=[CH:4][N:3]=1.C([NH:19][C:20](=[O:22])[O-:21])(C)(C)C.[C:23](=O)([O-])[O-].[Cs+].[Cs+].[CH2:29]1[CH2:33]OC[CH2:30]1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[C:29]([O:21][C:20]([NH:19][C:2]1[CH:7]=[C:6]([CH:8]([CH3:14])[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:5]=[CH:4][N:3]=1)=[O:22])([CH3:30])([CH3:33])[CH3:23]

Participants

Conditions

Temperature: 65 °C

Procedure

A mixture of ethyl 2-(2-chloropyridin-4-yl)propanoate (51) (1.55 g, 7.25 mmol), tert-butylcarbamate (2.55 g, 21.76 mmol), Pd2 dba3 (0.166 g, 0.181 mmol), caesium carbonate (3.55 g, 10.88 mmol) and Xantphos (0.210 g, 0.363 mmol) in THF (10 mL) was purged with nitrogen and heated at 65° C. for 48 hr. The mixture was then cooled to RT, diluted with water and extracted with ether. The ether layer was washed with water and brine and then dried (MgSO4) and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 100 g, 5-10% EtOAc in isohexane, gradient elution) to afford the title compound (52) (1.35 g, 61%): m/z 295 (M+H)+ (ES+).

Workup

customwas purged with nitrogen
temperatureThe mixture was then cooled to RT
additiondiluted with water
extractionextracted with ether
washThe ether layer was washed with water and brine
dry with materialdried (MgSO4)
customevaporated in vacuo
customThe residue was purified by flash column chromatography (SiO2, 100 g, 5-10% EtOAc in isohexane, gradient elution)

Sources & evidence

ORD record: ord-663ab8ce6d8147fdbdd8d3baf21496f6
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08299073B2

Reaction notes

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