Sodium Bicarbonate → N-(4-cyano-1-methoxy-piperidin-4-yl)-2-(2,5-dimethyl-phenyl)-N-hydroxy-acetamide

HRID 1473778Notes

Reaction equation

[OH:1][NH:2][C:3]1([C:11]#[N:12])[CH2:8][CH2:7][N:6]([O:9][CH3:10])[CH2:5][CH2:4]1.C(=O)([O-])O.[Na+].[CH3:18][C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][C:20]=1[CH2:26][C:27](Cl)=[O:28]>C(OCC)(=O)C.O>[C:11]([C:3]1([N:2]([OH:1])[C:27](=[O:28])[CH2:26][C:20]2[CH:21]=[C:22]([CH3:25])[CH:23]=[CH:24][C:19]=2[CH3:18])[CH2:4][CH2:5][N:6]([O:9][CH3:10])[CH2:7][CH2:8]1)#[N:12]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 4-hydroxyamino-1-methoxy-piperidine-4-carbonitrile (preparation example 11, step 2) (4.0 g, 23.4 mmol) and sodium hydrogen carbonate (3.0 g, 35.7 mmol) in ethyl acetate (35 ml) and water (25 ml) at 0° C. was added a solution of (2,5-dimethyl-phenyl)-acetyl chloride (4.2 g, 23.0 mmol) in ethyl acetate (35 ml) dropwise over one hour. The reaction mixture was stirred at 0° C. for one hour and at room temperature for two hours. The layers of the biphasic system were separated, the aqueous phase extracted with ethyl acetate (3×), the combined organic layers washed with brine, dried over sodium sulfate and concentrated. The oily residue was purified by chromatography on silica gel (gradient ethyl acetate/hexane 1:2→1:1→2:1). Yield: 1.55 g of N-(4-cyano-1-methoxy-piperidin-4-yl)-2-(2,5-dimethyl-phenyl)-N-hydroxy-acetamide (compound P3ii.2) as a white solid, mp 153-156° C.

Workup

customThe layers of the biphasic system were separated
extractionthe aqueous phase extracted with ethyl acetate (3×)
washthe combined organic layers washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated
customThe oily residue was purified by chromatography on silica gel (gradient ethyl acetate/hexane 1:2→1:1→2:1)

Sources & evidence

ORD record: ord-c4da35ca748c4391819dbf9e86814c5c
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018135B2

Reaction notes

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