Toluene → 1-((Benzyloxy)carbonyl)-3-methylpiperidine-2-carboxylic acid

HRID 60882

Reaction equation

Cl.[CH3:2][CH:3]1[CH2:8][CH2:7][CH2:6][NH:5][CH:4]1[C:9]([OH:11])=[O:10].Cl[C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14].C1(C)C=CC=CC=1>[OH-].[Na+].C1COCC1>[CH2:16]([O:15][C:13]([N:5]1[CH2:6][CH2:7][CH2:8][CH:3]([CH3:2])[CH:4]1[C:9]([OH:11])=[O:10])=[O:14])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

Conditions

Temperature: 0 °C

Procedure

3-Methylpiperidine-2-carboxylic acid hydrochloride (28.5 g, 31.6 mmol) was dissolved in (1:1) 2 M NaOH/THF (600 mL) and cooled to 0° C. Benzyl chloroformate (31.57 ml, 222 mmol) was then added dropwise and the reaction was stirred overnight. Toluene was then added and organic layer discarded to remove unreacted chloroformate. The aqueous layer was made acidic (pH=2) with conc. HCl and the product was extracted with EtOAc, dried (MgSO4), and concentrated in vacuo to give a crude residue which was used without further purification (41.6 g, 94.5%). 1H NMR (CDCl3, 400 MHz) δ 7.40-7.37 (m, 5H), 5.19 (m, 2H), 4.95-4.72 (m, 1H), 4.14-4.03 (m, 1H), 3.36-3.25 (m, 1H), 1.93-1.53 (m, 5H), 1.20-1.05 (m, 3H).

Workup

customto remove unreacted chloroformate
extractionthe product was extracted with EtOAc
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-0409c044ad724af4a04c943f9ed3440b
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440982B2

Linked notes

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