Diisopropylethylamine → 1,1-Dimethylethyl 4-[(5-cyclopropyl-3-fluoro-2-nitrophenyl)amino]-1-piperidinecarboxylate

HRID 447776Notes

Reaction equation

[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.C(N(C(C)C)CC)(C)C.[CH:24]1([C:27]2[CH:28]=[C:29](F)[C:30]([N+:34]([O-:36])=[O:35])=[C:31]([F:33])[CH:32]=2)[CH2:26][CH2:25]1>CN(C)C=O>[CH:24]1([C:27]2[CH:32]=[C:31]([F:33])[C:30]([N+:34]([O-:36])=[O:35])=[C:29]([NH:1][CH:2]3[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]3)[CH:28]=2)[CH2:26][CH2:25]1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of 1,1-dimethylethyl 4-amino-1-piperidinecarboxylate (1 eq., 1.51 mmol, 302 mg) in dry dimethylformamide (10 ml), diisopropylethylamine (1 eq., 1.51 mmol, 0.26 ml) and 5-cyclopropyl-1,3-difluoro-2-nitrobenzene (D25, 1 eq., 1.51 mmol, 300 mg) were added at room temperature and the mixture was stirred under argon at 120° C. overnight. The crude mixture was then cooled to room temperature and poured onto water (10 ml). The aqueous solution was extracted with ethyl acetate (3×100 ml) and the organics were combined and washed with water and brine alternately (5×100 ml), dried over Na2SO4, filtered and the solvent was evaporated to afford the crude compound which was purified by chromatography (30% ethyl acetate-n-hexane 60%) to yield the title compound; 300 g, 0.79 mmol, 52%, M−−H=378.

Workup

additionpoured onto water (10 ml)
extractionThe aqueous solution was extracted with ethyl acetate (3×100 ml)
washwashed with water and brine alternately (5×100 ml)
dry with materialdried over Na2SO4
filtrationfiltered
customthe solvent was evaporated
customto afford the crude compound which
customwas purified by chromatography (30% ethyl acetate-n-hexane 60%)

Sources & evidence

ORD record: ord-699d35e1c38b49b0b9e170c42d6ba4d8
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481566B2

Reaction notes

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