Ethyl bromopyruvate → Ethyl cis(+/-)-2-(4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidin-1-yl)-1,3-oxazole-4-carboxylate

HRID 1425078Notes

Reaction equation

Br[CH2:2][C:3](=O)[C:4]([O:6][CH2:7][CH3:8])=[O:5].C(=O)(O)[O-].[Na+].[C:15]([N:18]1[CH2:23][CH2:22][C@H:21]([NH:24][C:25](=[O:34])[O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C@H:20]([O:35][CH3:36])[CH2:19]1)(=[O:17])[NH2:16]>C1COCC1>[CH2:27]([O:26][C:25]([NH:24][C@H:21]1[CH2:22][CH2:23][N:18]([C:15]2[O:17][CH:2]=[C:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])[N:16]=2)[CH2:19][C@H:20]1[O:35][CH3:36])=[O:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

Conditions

Temperature: 70 °C

Procedure

Ethyl bromopyruvate (2.93 g, 15 mmol) and sodium bicarbonate (2.10 g, 25 mmol) were added to a solution of cis(±)-benzyl (1-carbamoyl-3-methoxypiperidin-4-yl)carbamate obtained in Example (103b) (1.4 g, 4.56 mmol) in THF (30 mL), and the mixture was stirred at 70° C. for three hours. The insoluble matter was filtered off, followed by dilution with ethyl acetate. This was washed with water and brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution solvent: ethyl acetate/hexane=1/4, 1/2, 1/1, 2/1, 4/1) to obtain 1.46 g of the title compound as a colorless solid (79%).

Workup

filtrationThe insoluble matter was filtered off
washThis was washed with water and brine
dry with materialdried over anhydrous magnesium sulfate
concentrationconcentrated under reduced pressure
customThe resulting residue was purified by silica gel column chromatography (elution solvent: ethyl acetate/hexane=1/4, 1/2, 1/1, 2/1, 4/1)

Sources & evidence

ORD record: ord-4688cff090194cdf8ef879d47c673b92
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08927588B2

Reaction notes

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