Ethyl Acetate → (3-Isopropoxy-4-nitrophenyl)(1-methylpiperidin-4-yl)amine

HRID 518855Notes

Reaction equation

C(=O)([O-])[O-].[K+].[K+].[NH2:7][CH:8]1[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]1.F[C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[C:18]([O:25][CH:26]([CH3:28])[CH3:27])[CH:17]=1.C(OCC)(=O)C>CS(C)=O>[CH:26]([O:25][C:18]1[CH:17]=[C:16]([NH:7][CH:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[CH:21]=[CH:20][C:19]=1[N+:22]([O-:24])=[O:23])([CH3:28])[CH3:27]

Participants

Conditions

Temperature: 120 °C

Procedure

1.7 g of potassium carbonate and 1.0 g of 4-amino-1-methylpiperidine are successively added to a solution of 1.6 g of 4-fluoro-2-isopropoxy-1-nitrobenzene in 13.5 ml of dimethyl sulfoxide. The reaction mixture is heated at 120° C. for 3 h and is then cooled to ambient temperature and poured into a mixture of 150 ml of ice-cold water and 100 ml of ethyl acetate. After settling out, the organic phase is separated and the aqueous phase is extracted twice with 70 ml of ethyl acetate. The organic extracts are combined, dried over magnesium sulfate and then concentrated to dryness under reduced pressure. The residue is purified by chromatography on a 90 g silica cartridge, elution being carried out with a 97.5/2/0.5 v/v/v dichloromethane/methanol/20% aqueous ammonia mixture at a flow rate of 50 ml/min, so as to obtain 1.5 g of (3-isopropoxy-4-nitrophenyl)(1-methylpiperidin-4-yl)amine in the form of a bright yellow oil.

Workup

temperatureis then cooled to ambient temperature
customthe organic phase is separated
extractionthe aqueous phase is extracted twice with 70 ml of ethyl acetate
dry with materialdried over magnesium sulfate
concentrationconcentrated to dryness under reduced pressure
customThe residue is purified by chromatography on a 90 g silica cartridge, elution

Sources & evidence

ORD record: ord-74921dd52e7d4e90a903b6da99cf7cae
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115140B2

Reaction notes

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