Tetrahydrofuran → 5-Oxo-6-(pyridine-2-yl)-1,2,3,5-tetrahydroindolizine-8-carboxylic acid

HRID 253119Notes

Reaction equation

FC(F)(F)S(O[C:7]1[C:8](=[O:20])[N:9]2[C:13](=[C:14]([C:16](=[O:19])CC)[CH:15]=1)[CH2:12][CH2:11][CH2:10]2)(=O)=O.C[Sn](C)(C)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1.[Li+].[Cl-].C1C[O:38]CC1>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:20]=[C:8]1[C:7]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=2)=[CH:15][C:14]([C:16]([OH:19])=[O:38])=[C:13]2[N:9]1[CH2:10][CH2:11][CH2:12]2

Participants

Conditions

Temperature: 160 °C

Procedure

A mixture of 5-oxo-8-propionyl-1,2,3,5-tetrahydroindolizin-6-yl trifluoromethanesulfonate (0.50 g, 1.46 mmol), 2-trimethylstannyl pyridine (0.46 g, 1.90 mmol), LiCl (0.17 g, 4.38 mmol), and (Ph3P)4Pd (0.12 g, 0.11 mmol) in THF (10 mL) was heated by Microwave Synthesizer at 160° C. for 20 min. The reaction was cooled, diluted with H2O and extracted into EtOAc (3×). The organic layers were combined, dried over MgSO4 and concentrated. The concentrate was triturated in ether to give the salt of the title compound as a light green solid. The solid was dissolved in MeOH (5 mL), to which was added 2 eq. of 1N NaOH and the mixture was stirred for 2 h. The mixture was concentrated, taken up in H2O, neutralized by 10% HCl, extracted with CH2Cl2 (3×), dried over MgSO4, concentrated to give the title compound as a light yellow oil (0.32 g, 85%). MS (m/z, M+1): 257.1.

Workup

temperatureThe reaction was cooled
extractionextracted into EtOAc (3×)
dry with materialdried over MgSO4
concentrationconcentrated
customThe concentrate was triturated in ether

Sources & evidence

ORD record: ord-4d969dc710af45ce8adb4ff4c94ae0e6
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07872009B2

Reaction notes

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