Hydrochloric Acid → 1-(4-Chloro-3-methoxyphenyl)piperidin-4-one

HRID 1804852Notes

Reaction equation

HRID 1804852 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:17][CH2:16][C:11]3(OCC[O:12]3)[CH2:10][CH2:9]2)=[CH:4][C:3]=1[O:18][CH3:19].Cl.[OH-].[Na+]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:17][CH2:16][C:11](=[O:12])[CH2:10][CH2:9]2)=[CH:4][C:3]=1[O:18][CH3:19]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 685538928-(4-Chloro-3-methoxyphenyl)-1,4-dioxa-8-azaspiro[4.5]decane

Product 1

HCID 685574401-(4-Chloro-3-methoxyphenyl)piperidin-4-oneYield 99.7%

Procedure

A sample of 8-(4-chloro-3-methoxyphenyl)-1,4-dioxa-8-azaspiro[4.5]decane (1.1 g, 2.89 mmol) was treated with 6 M HCl (15 mL) and heated at reflux for 3 h. The mixture was cooled to RT and made basic with 2 M NaOH. The basic mixture was extracted with EtOAc. The extract was dried (Na2SO4) and concentrated on a rotary evaporator to give the crude product. The crude product was purified by flash chromatography (40 g silica gel cartridge and gradient elution from 10 to 40% EtOAc/hexanes) to give 1-(4-chloro-3-methoxyphenyl)piperidin-4-one (690 mg, 2.88 mmol, 51.5% yield) as a yellow oil. 1H-NMR (400 MHz, CDCl3) δ ppm 7.21 (1 H, d, J=8.57 Hz), 6.52 (1 H, d, J=2.64 Hz), 6.47 (1 H, dd, J=8.68, 2.75 Hz), 3.88 (3 H, s), 3.57 (4 H, t, J=6.04 Hz), 2.55 (4 H, t, J=6.04 Hz).

Workup

  1. temperatureheated
  2. temperatureat reflux for 3 h
  3. extractionThe basic mixture was extracted with EtOAc
  4. dry with materialThe extract was dried (Na2SO4)
  5. concentrationconcentrated on a rotary evaporator
  6. customto give the crude product
  7. customThe crude product was purified by flash chromatography (40 g silica gel cartridge and gradient elution from 10 to 40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-7777c24561474cd29409724ebe46d3b0
Source dataset
uspto-grants-2013_01
Patent number
US08354432B2

Reaction notes

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