Pyridine → Methyl 1-(4-formyl-2-(5-methylisoxazole-3-carboxamido)phenyl)piperidine-4-carboxylate

HRID 1801587Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][C:3]=1[N:10]1[CH2:15][CH2:14][CH:13]([C:16]([O:18][CH3:19])=[O:17])[CH2:12][CH2:11]1.N1C=CC=CC=1.[CH3:26][C:27]1[O:31][N:30]=[C:29]([C:32](Cl)=[O:33])[CH:28]=1>C(Cl)Cl.CCOC(C)=O>[CH:8]([C:6]1[CH:5]=[CH:4][C:3]([N:10]2[CH2:11][CH2:12][CH:13]([C:16]([O:18][CH3:19])=[O:17])[CH2:14][CH2:15]2)=[C:2]([NH:1][C:32]([C:29]2[CH:28]=[C:27]([CH3:26])[O:31][N:30]=2)=[O:33])[CH:7]=1)=[O:9]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of methyl 1-(2-amino-4-formylphenyl)piperidine-4-carboxylate 59 (0.488 g, 1.9 mmol) in DCM (10 mL) at 0° C. was added pyridine (0.300 mL, 3.7 mmol) and 5-methylisoxazole-3-carbonyl chloride (0.185 g, 1.3 mmol). The reaction mixture was stirred at 0° C. for 30 min, additional acid chloride (88 mg) was added and stirring was continued at 0° C. After 30 min, the reaction mixture was diluted with EtOAc, washed with saturated NaHCO3 (1×), brine (1×), dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash column chromatography on silica gel (eluted with 20% to 50% EtOAc in hexanes) gave methyl 1-(4-formyl-2-(5-methylisoxazole-3-carboxamido)phenyl)piperidine-4-carboxylate 60 (0.268 g, 39% yield) as a pale yellow solid. Mass spectrum: calculated for C19H21N3O5 371.2. found 372.2 (M++1).

Workup

stirringstirring
customwas continued at 0° C
waitAfter 30 min
washwashed with saturated NaHCO3 (1×), brine (1×)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customPurification by flash column chromatography on silica gel (eluted with 20% to 50% EtOAc in hexanes)

Sources & evidence

ORD record: ord-3fb9a0a0b5d14e36907e5211e01e1242
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08349831B2

Reaction notes

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