Methyl iodide → 2-methyl-3-(N-Boc-piperidine-4-yl)-propionic acid methyl ester

HRID 1691856Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:19])[CH2:4][CH2:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1.[CH3:20][Si]([N-][Si](C)(C)C)(C)C.[Na+].CI>O1CCCC1>[CH3:1][O:2][C:3](=[O:19])[CH:4]([CH3:20])[CH2:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[O:13])[CH2:8][CH2:7]1

Participants

Conditions

Temperature: -78 °C

Procedure

3-(N-Boc-piperidine-4-yl)-propionic acid methyl ester (2.0 g, 7.38 mmol) from above was dissolved in tetrahydrofuran (50 mL). The solution was cooled to −78° C. and sodium bis(trimethylsilyl)amide (1.0 M, 9.0 mL) was added. The mixture was stirred at −78° C. for 1 hr and methyl iodide (1.2 mL, 19.5 mmol) was added. The mixture was warmed to room temperature and stirred for 2 hrs. The mixture was extracted with ether and washed with dilute hydrochloric acid. The organic layer was dried, filtered and concentrated. The residue was purified using flash chromatography (eluting with ethyl acetate and hexanes) to give 2-methyl-3-(N-Boc-piperidine-4-yl)-propionic acid methyl ester as an oil (789 mg).

Workup

temperatureThe mixture was warmed to room temperature
stirringstirred for 2 hrs
extractionThe mixture was extracted with ether
washwashed with dilute hydrochloric acid
customThe organic layer was dried
filtrationfiltered
concentrationconcentrated
customThe residue was purified
washflash chromatography (eluting with ethyl acetate and hexanes)

Sources & evidence

ORD record: ord-9a4deedac40b4f63a9c1bcdeb98616a8
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08153644B2

Reaction notes

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