Trifluoroacetic acid → Ethyl 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-carboxylate

HRID 1808338Notes

Reaction equation

FC(F)(F)C(O)=O.N1([C:13]23[O:28][N:27]=[C:26]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH:14]2[CH2:15][N:16](C(OC(C)(C)C)=O)[CH2:17][CH2:18]3)CCCC1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[O:28]1[C:13]2[CH2:18][CH2:17][NH:16][CH2:15][C:14]=2[C:26]([C:29]([O:31][CH2:32][CH3:33])=[O:30])=[N:27]1

Participants

Conditions

Temperature: 0 °C

Procedure

Trifluoroacetic acid (6.67 ml, 89.9 mmol) was added at 0° C. to a solution of 5-tert-butyl 3-ethyl 7a-(pyrrolidin-1-yl)-3a,4,7,7a-tetrahydroisoxazolo[4,5-c]pyridine-3,5(6H)-dicarboxylate (5.5 g, 14.98 mmol) in DCM (100 ml), and the mixture was stirred for 16 hours under reflux. Cooling to 0° C. was then carried out and NaHCO3 solution was added. The phases were separated and the aqueous phase was extracted with dichloromethane. The combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo. Purification of the crude product was carried out by column chromatography (silica gel, 16% methanol in ethyl acetate). Yield: 62% [Alternatively, ethyl 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-carboxylate A-06 can be synthesised as described in WO2006105945.]

Workup

temperatureunder reflux
customThe phases were separated
extractionthe aqueous phase was extracted with dichloromethane
dry with materialThe combined organic phases were dried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customPurification of the crude product
customYield: 62% [Alternatively, ethyl 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-carboxylate A-06 can be synthesised

Sources & evidence

ORD record: ord-ad1b1b1750894bf6ae45824746de2b18
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08357717B2

Reaction notes

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