Methyl iodide → 4-Methoxy-4-(4-pyrimidin-2-yl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1038063Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([OH:26])([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[N:25]=[CH:24][CH:23]=[CH:22][N:21]=3)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:27]I.[H-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]([O:26][CH3:27])([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[N:25]=[CH:24][CH:23]=[CH:22][N:21]=3)=[CH:16][CH:15]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 0 °C

Procedure

4-Hydroxy-4-(4-pyrimidin-2-yl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester 81 (138 mg, 0.39 mmol) was dissolved in DMF (2 mL) and cooled to 0° C. MeI (0.1 mL) was added followed by the addition of NaH (26 mg, 60% suspension in mineral oil). After 30 min at 0° C., the reaction was quenched with sat. NH4Cl and extracted with ethyl acetate. The combined organic layers was washed with brine, dried and concentrated in vacuo. The residue was purified with prep TLC plates (developing with 50% ethyl acetate/hexanes) to yield a colorless film (80 mg) as the title compound.

Workup

customthe reaction was quenched with sat. NH4Cl
extractionextracted with ethyl acetate
washThe combined organic layers was washed with brine
customdried
concentrationconcentrated in vacuo
customThe residue was purified with prep TLC plates (developing with 50% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-6dce08254b2c4b69afc6009b1e001d17
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08546404B2

Reaction notes

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