Trifluoroacetic acid → Ethyl pyrrolo[1,2-a]pyrazine-3-carboxylate

HRID 25157Notes

Reaction equation

C(O)(C(F)(F)F)=O.P(Cl)(Cl)(Cl)=O.C(O[CH:16](OCC)[C@@H:17]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:18]=[CH:19][C:20]1[NH:21][CH:22]=[CH:23][CH:24]=1)C.C([O-])(O)=O.[Na+]>ClCCCl>[CH:19]1[C:20]2[N:21]([CH:22]=[CH:23][CH:24]=2)[CH:16]=[C:17]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:18]=1

Participants

Conditions

Temperature: 65 °C

Procedure

To a hot (65° C.) solution of TFA (44 mL, 510 mmol) and phosphorus oxychloride (39.0 g, 140 mmol) is added drop-wise a solution of ethyl 3-ethoxy-O-ethyl-N-(1H-pyrrol-2-ylmethylene)serinate (Dekhane, M; Potier, P; Dodd, R. H. Tetrahedron, 49, 1993, 8139-46.) (9.6 g, 28.0 mmol) in anhydrous 1,2-dichloroethane (200 mL). The black mixture is allowed to stir at 65° C. for 18 h at which point it is cooled to rt and neutralized with sat. NaHCO3 and solid NaHCO3 to pH ˜9. The phases are separated and the basic phase extracted with EtOAc (4×100 mL). The organic phases are combined, washed with brine, dried over Na2SO4, filtered, and concentrated to give a black oil that is purified with silica gel chromatography (35% EtOAc/heptanes to 50% over several liters) to give a light brown solid for ethyl pyrrolo[1,2-a]pyrazine-3-carboxylate. Yield 24%. HRMS (FAB) calcd for C10H10N2O2+H 191.0820, found 191.0823.

Workup

customThe phases are separated
extractionthe basic phase extracted with EtOAc (4×100 mL)
washwashed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customto give a black oil that
customis purified with silica gel chromatography (35% EtOAc/heptanes to 50% over several liters)

Sources & evidence

ORD record: ord-e4135f60fd404cbf859c49ebfe10990d
Source dataset: uspto-grants-2005_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06858613B2

Reaction notes

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