p-Fluoronitrobenzene → Tert-butyl 4-(4-nitrophenoxy)piperidine-1-carboxylate

HRID 557788Notes

Reaction equation

HRID 557788 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[C:11]([N:18]1[CH2:23][CH2:22][CH:21]([OH:24])[CH2:20][CH2:19]1)([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].[H-].[Na+]>C1COCC1>[C:14]([O:13][C:11]([N:18]1[CH2:23][CH2:22][CH:21]([O:24][C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)[CH2:20][CH2:19]1)=[O:12])([CH3:17])([CH3:15])[CH3:16]

Participants

5

Reactant 3

HCID 9590p-FluoronitrobenzeneHCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 2794776Tert-butyl 4-(4-nitrophenoxy)piperidine-1-carboxylateYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-fluoronitrobenzene (1.41 g, 10 mmol) in THF (50 mL) was added N-Boc-4-hydroxypiperidine (2.01 g, 10 mmol) and sodium hydride (60% in mineral oil, 583 mg, 14.5 mmol). The mixture was stirred at room temperature for 14 hrs. After purification through flash column chromatography, 4-(4-nitro-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester (2.51 g, 78% yield) was obtained as a solid. This nitro compound was hydrogenated to the corresponding amine and coupled with 2-phenyl-5-trifluoromethyloxazole-4-carboxylic acid to give 4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenoxy}-piperidine-1-carboxylic acid tert-butyl ester. LC-MS showed a single peak with a retention time of 4.08 min. LRMS calcd for C27H28F3N3O5 (M+1) 532.20, obsd 532.1

Workup

  1. customAfter purification through flash column chromatography

Sources & evidence

ORD record
ord-7e6deca8e41a4f2ca77d2f8597127e82
Source dataset
uspto-grants-2011_11
Patent number
US08058299B2

Reaction notes

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