Tert-butyl 4-hydroxypiperidine-1-carboxylate → Tert-butyl 4-(2-(difluoromethoxy)-4-nitrophenoxy)piperidine-1-carboxylate

HRID 633430Notes

Reaction equation

HRID 633430 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[O:11][CH:12]([F:14])[F:13].CC(C)([O-])C.[K+].[C:21]([N:28]1[CH2:33][CH2:32][CH:31]([OH:34])[CH2:30][CH2:29]1)([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22]>C1COCC1>[F:13][CH:12]([F:14])[O:11][C:3]1[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[O:34][CH:31]1[CH2:30][CH2:29][N:28]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:33][CH2:32]1

Participants

5

Reactant 3

HCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 23665647Potassium tert-butoxideHCID 534032881-Chloro-2-(difluoromethoxy)-4-nitrobenzene

Product 1

HCID 86704525Tert-butyl 4-(2-(difluoromethoxy)-4-nitrophenoxy)piperidine-1-carboxylateYield 28%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Using similar procedure detailed below for Compound 133, but using 1-chloro-2-(difluoromethoxy)-4-nitrobenzene (prepared according to US patent application no. 2010/090875) (1.12 g, 5.0 mmol), potassium tert-butoxide (1.18 g, 10.0 mmol) and N-Boc-4-hydroxypiperidine (2.0 g, 10.0 mmol) in THF (30 mL) was stirred for a weekend at room temperature to give the product (406 mg, 28% yield) after workup and purification by column chromatography on silica gel using EtOAc/heptane (1:9 to 1:1) as eluent. The product was about 70% purity by LC/MS and 1H NMR.

Workup

  1. customprepared

Sources & evidence

ORD record
ord-ea1f87dfcd1c456bb4a30a9c5d5dc5a9
Source dataset
uspto-grants-2016_04
Patent number
US09321763B2

Reaction notes

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