Methyl iodide → HCID 89691688, compound

HRID 80752Notes

Reaction equation

[OH:1][C@H:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][C@H:3]1[CH3:15].[H-].[Na+].[CH3:18]I>CN(C=O)C>[CH3:18][O:1][C@H:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][C@H:3]1[CH3:15]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of racemic (cis)-tert-butyl 4-hydroxy-3-methylpiperidine-1-carboxylate (310 mg, 1.44 mmol) (CAS#955028-93-0; prepared as described in US 20070249589)] in DMF (5 mL) at 0° C. was added NaH (60% dispersion in mineral oil, 75 mg, 1.87 mmol). The reaction mixture was stirred at 0° C. for 10 minutes and MeI (0.13 mL, 2.02 mmol) was added. After 2 h the reaction was quenched with saturated aqueous NH4Cl. The aqueous phase was washed three times with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated. The resulting residue was purified by silica gel flash chromatography (0-100% EtOAc/heptanes) to provide racemic (cis)-tert-butyl 4-methoxy-3-methylpiperidine-1-carboxylate. 1H NMR (400 MHz, CDCl3) δ ppm 3.36-3.50 (m, 6 H), 3.34 (dt, J=6.6, 3.3 Hz, 1 H), 3.22-3.29 (m, 1 H), 1.78-1.96 (m, 2 H), 1.49 (s, 9 H), 0.95 (d, J=6.8 Hz, 3 H).

Workup

customAfter 2 h the reaction was quenched with saturated aqueous NH4Cl
washThe aqueous phase was washed three times with EtOAc
washThe combined organic extracts were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe resulting residue was purified by silica gel flash chromatography (0-100% EtOAc/heptanes)

Sources & evidence

ORD record: ord-d5cdcaccf8ed4859915a2f6b57826b42
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846656B2

Reaction notes

Loading…