Sodium hydride → tert-Butyl 4-(5-cyanopyridin-2-yloxy)piperidine-1-carboxylate

HRID 427466Notes

Reaction equation

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

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 1-(t-butyloxycarbonyl)-4-piperidinol (600 mg) in dry DMF (20 mL) was added sodium hydride (0.24 g, 50% dispersion in oil) and stirred under argon for 1 hour. 2-Chloro,5-cyanopyridine (0.44 g) was added and the mixture was heated at 70° C. overnight. The reaction was quenched by pouring into water and extracted with diethyl ether. The extract was washed with water, brine, dried (MgSO4) and evaporated. The residue was then chromatographed on silica gel eluting with a mixture of dichloromethane (25%) in isohexane increasing to dichloromethane. The residue was recrystallised from isohexane to afford 1-(t-butyloxycarbonyl),4-(5-cyano,2-pyridyloxy)piperidine (400 mg) as a colourless crystalline solid; NMR: (CDCl3) 1.46 (s,9H), 164-182 (m,2H), 1.92-2.09 (m,2H), 3.21-3.36 (m,2H), 3.70-3.84 (m,2H), 5.28 (m,1H), 6.78 (d,1H), 7.77 (dd,1H): MS: m/z 304 (MH)+.

Workup

customThe reaction was quenched
additionby pouring into water
extractionextracted with diethyl ether
washThe extract was washed with water, brine
dry with materialdried (MgSO4)
customevaporated
customThe residue was then chromatographed on silica gel eluting with a mixture of dichloromethane (25%) in isohexane increasing to dichloromethane
customThe residue was recrystallised from isohexane

Sources & evidence

ORD record: ord-b8b3f676ecbe4fab9d18a7a0c9975816
Source dataset: uspto-grants-2001_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06313127B1

Reaction notes

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