Sodium Carbonate → Phenylmethyl 3-(aminocarbonyl)-3-methyl-1-piperidinecarboxylate

HRID 1257747Notes

Reaction equation

Cl.[CH3:2][C:3]1([C:9]([NH2:11])=[O:10])[CH2:8][CH2:7][CH2:6][NH:5][CH2:4]1.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+].Cl[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26]>O>[CH2:28]([O:27][C:25]([N:5]1[CH2:6][CH2:7][CH2:8][C:3]([C:9](=[O:10])[NH2:11])([CH3:2])[CH2:4]1)=[O:26])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 3-Methyl-piperidine-3-carboxylic acid amide hydrochloride (740 mg, 4.1 mmol) in a cosolvent of 1,4-dioxane and water (12 mL, v:v=5:1) was added sodium carbonate (1.6 g, 15 mmol). The mixture was cooled to 0° C., benzyl chloroformate (900 mg, 0.53 mmol) was added, and the mixture was allowed to stir at room temperature for 3 h. LCMS showed starting material was consumed. The volatile components were removed, and the residue was extracted with ethyl acetate, purified by column chromatography (eluting with 10% methanol in dichloromethane) to give 600 mg (53%) of 3-Carbamoyl-3-methyl-piperidine-1-carboxylic acid benzyl ester. LCMS (Method K, ESI): RT=1.18 min, m+Na=298.8; 1H NMR (400 MHz, CDCl3) δ: 7.32-7.23 (m, 5H), 5.07-5.03 (m, 2H), 4.30-4.10 (m, 1H), 4.10-3.90 (m, 1H), 3.10-2.40 (m, 2H), 1.65-1.75 (m, 2H), 1.60-1.30 (m, 2H), 1.25-1.15 (m, 1H), 1.09 (s, 3H).

Workup

customwas consumed
customThe volatile components were removed
extractionthe residue was extracted with ethyl acetate
custompurified by column chromatography (eluting with 10% methanol in dichloromethane)

Sources & evidence

ORD record: ord-9f8fb9ad67004763bed63166227dd773
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08461328B2

Reaction notes

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