Water → Tert-butyl 4-(4-nitrophenoxy)piperidine-1-carboxylate

HRID 1779076Notes

Reaction equation

HRID 1779076 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[OH:11][CH:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1.CC(C)([O-])C.[K+].O>CS(C)=O.CCOC(C)=O>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([O:11][CH:12]2[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH2:17]2)=[CH:3][CH:4]=1)([O-:10])=[O:9]

Participants

7

Reactant 4

HCID 962WaterHCID 9590p-FluoronitrobenzeneHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 2794776Tert-butyl 4-(4-nitrophenoxy)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Fluoro-nitrobenzene (0.728 mL, 6.96 mmol) was added to a solution of tert-butyl 4-hydroxypiperidine-1-carboxylate (A110) (1.40 g, 6.96 mmol) and potassium tert-butoxide (1.09 g, 9.74 mmol) in anhydrous DMSO (7.5 mL) and the resulting mixture was stirred for 2 hours at room temperature. Water and EtOAc were added to the mixture and the phases were separated. The aqueous phase was extracted with EtOAc, then the combined organic extracts were washed with water, brine and dried over Na2SO4. The volatiles were evaporated under reduced pressure and the residue was adsorbed onto silica gel and purified by column chromatography (SiO2 cartridge, 0-15% EtOAc in cyclohexane) to give the title compound A111 as an oil (2.20 g, 98%); 1H NMR (300 MHz, CDCl3); δ 8.09 (d, J=9.4 Hz, 2H), 6.91 (d, J=9.3 Hz, 2H), 4.58 (m, 1H), 3.65 (m, 2H), 3.33 (m, 2H), 1.92 (m, 2H), 1.72 (m, 2H), 1.41 (s, 9H). LCMS-B: rt 8.22 min; m/z 323.3 [M+H]+.

Workup

  1. customthe phases were separated
  2. extractionThe aqueous phase was extracted with EtOAc
  3. washthe combined organic extracts were washed with water, brine
  4. dry with materialdried over Na2SO4
  5. customThe volatiles were evaporated under reduced pressure
  6. custompurified by column chromatography (SiO2 cartridge, 0-15% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-0098e7430fae4f978af6bea7d4d01f1d
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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