Sodium hydride → 2-{(R)-1-[(3S,4S)-1-Benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-ethoxy}-5-chloro-pyridine

HRID 2191112Notes

Reaction equation

[H-].[Na+].[CH2:3]([N:10]1[CH2:15][CH2:14][C@H:13]([C@@H:16]([OH:18])[CH3:17])[C@@H:12]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)[CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][N:28]=1>CN(C=O)C>[CH2:3]([N:10]1[CH2:15][CH2:14][C@H:13]([C@H:16]([O:18][C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][N:28]=2)[CH3:17])[C@@H:12]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)[CH2:11]1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

Conditions

Temperature: 40 °C

Procedure

A mixture of 69 mg (1.7 mmol) NaH (55% suspension in mineral oil), 359 mg (1.08 mmol) (S)-1-[(3S,4S)-1-benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-ethanol and 225 mg (1.52 mmol) 2,5-dichloropyridine in 2 mL DMF was stirred for 20 h at 40° C. Further 0.2 eq. 2,5-dichloropyridine was added and stirring was continued for 20 h at 60° C. After evaporation the residue was purified by column chromatography on silica eluting with a gradient formed from ethyl acetate and heptane to afford after evaporation of the product containing fractions 205 mg (43%) of the title compound as colorless viscous oil. MS (m/e): 441.1 [(M+H)+]

Workup

stirringstirring
waitwas continued for 20 h at 60° C
customAfter evaporation the residue
customwas purified by column chromatography on silica eluting with a gradient
customformed from ethyl acetate and heptane
customto afford
customafter evaporation of the product
additioncontaining fractions 205 mg (43%) of the title compound as colorless viscous oil

Sources & evidence

ORD record: ord-758aaf18f7d645138f906ff465522825
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08324248B2

Reaction notes

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