Phthalimide potassium salt → tert-Butyl 4-(6-amino-3,5-difluoropyridin-2-yl)piperazine-1-carboxylate

HRID 912840Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([F:20])=[CH:18][C:17]([F:21])=[C:16](F)[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(=O)[NH:27]C(=O)C2=CC=CC=C12.[K]>CN(C=O)C.O>[NH2:27][C:16]1[N:15]=[C:14]([N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)[C:19]([F:20])=[CH:18][C:17]=1[F:21]

Participants

Conditions

Temperature: 140 °C

Procedure

A mixture of 4-(3,5,6-trifluoro-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester (1.59 g, 5 mmol, Example 39a), potassium phthalimide (0.93 g, 5 mmol, Aldrich) in DMF (20 mL) was heated at 140° C. with stirring for 16 h. The reaction mixture was cooled to room temperature, diluted with water (60 mL) and extracted with EtOAc (2×70 mL). The combined organic extracts were dried over Na2SO4, and filtered. The filtrate was evaporated and the residue was purified by silica gel column chromatography, eluting with 20% EtOAc in hexane to give the title compound as a yellow solid. MS (ESI, pos. ion) m/z: 315 (M+1).

Workup

temperatureThe reaction mixture was cooled to room temperature
extractionextracted with EtOAc (2×70 mL)
dry with materialThe combined organic extracts were dried over Na2SO4
filtrationfiltered
customThe filtrate was evaporated
customthe residue was purified by silica gel column chromatography
washeluting with 20% EtOAc in hexane

Sources & evidence

ORD record: ord-3e5d602ceecf4ee3a70a059a46b269d3
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026241B2

Reaction notes

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