Cesium carbonate → methyl 4-(3,4,6,7,8,8a-hexahydro-1H-pyrrolo[2,1-c]pyrazin-2-yl)benzoate

HRID 16807

Reaction equation

I[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(C1CCCCC1=O)(=O)C.[CH2:28]1[NH:33][CH2:32][CH2:31][N:30]2[CH2:34][CH2:35][CH2:36][CH:29]12>CN(C=O)C.[Cu]I>[CH2:28]1[CH:29]2[CH2:36][CH2:35][CH2:34][N:30]2[CH2:31][CH2:32][N:33]1[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 90 °C

Procedure

Methyl 4-iodobenzoate (2.076 g, 7.92 mmol), cesium carbonate (5.16 g, 15.85 mmol), 2-acetylcyclohexanone (0.209 mL, 1.58 mmol) and copper(I) iodide (0.075 g, 0.40 mmol) were added to a stirred solution of 1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine (1 g, 7.92 mmol) in DMF (20 mL) under nitrogen. The resulting suspension was stirred at 90° C. for 20 h. The reaction mixture was evaporated to dryness and redissolved in a mixture of methanol and water. The crude product was purified by ion exchange chromatography, using a SCX column. The desired product was eluted from the column using 3.5M NH3/MeOH and pure fractions were evaporated to dryness to afford methyl 4-(3,4,6,7,8,8a-hexahydro-1H-pyrrolo[2,1-c]pyrazin-2-yl)benzoate (1.243 g, 60.2%) as a brown gum.

Workup

customThe reaction mixture was evaporated to dryness
dissolutionredissolved in a mixture of methanol and water
customThe crude product was purified by ion exchange chromatography
washThe desired product was eluted from the column
customwere evaporated to dryness

Sources & evidence

ORD record: ord-7f3f75c7e3ed4cb5b90be7ec540c59d0
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07737149B2

Linked notes

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