Tetrahydrofuran → N-[(2,2-Dimethoxy)ethyl]-N-(2-pyridyl)cyclohexanecarboxamide

HRID 649806Notes

Reaction equation

HRID 649806 reaction equation
[CH3:1][O:2][CH:3]([O:12][CH3:13])[CH2:4][NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=1.[CH2:14]([Li])[CH2:15][CH2:16]C.[O:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1>>[CH3:1][O:2][CH:3]([O:12][CH3:13])[CH2:4][N:5]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=1)[C:23]([CH:22]1[CH2:16][CH2:15][CH2:14][CH2:20][CH2:21]1)=[O:19]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 217139332-(2,2-Dimethoxyethylamino)pyridineHCID 178418339Butyllithium

Product 1

HCID 21713913N-[(2,2-Dimethoxy)ethyl]-N-(2-pyridyl)cyclohexanecarboxamideYield 78%

Conditions

Temperature
0 °C

Procedure

To a solution comprising 5.97 g 2-(2,2-dimethoxyethylamino)pyridine (prepared as described by I. Kaye, in J. Am. Chem. Soc., 73, 5467 (195 1)) in 40 mL tetrahydrofurane, stirred under a nitrogen atmosphere at 0° C., was added, in a dropwise manner, 13.1 mL butyl lithium (2.5 M, in hexane). This was followed by removal of the cooling bath, and stirring of the obtained mixture for 1 h, at room temperature. There was then added, in a dropwise manner, 4.46 mL cyclohexanecarbonyl chloride. Then, after 5.5 h stirring at room temperature, 2 mL methanol was added. The solution was then evaporated to dryness under a vacuum, yielding a chestnut-colored oil; this product was then purified by flash chromatography (chloroform—ethyl acetate 7:3). The fractions containing the product were evaporated to dryness affording 8.3 g of Compound 1A (yield 78%); this substance was suitable for use in subsequent reactions with no additional purification processing.

Workup

  1. customThis was followed by removal of the cooling bath
  2. stirringstirring of the obtained mixture for 1 h, at room temperature
  3. additionThere was then added, in a dropwise manner, 4.46 mL cyclohexanecarbonyl chloride
  4. stirringThen, after 5.5 h stirring at room temperature
  5. addition2 mL methanol was added
  6. customThe solution was then evaporated to dryness under a vacuum
  7. customyielding a chestnut-colored oil
  8. customthis product was then purified by flash chromatography (chloroform—ethyl acetate 7:3)
  9. additionThe fractions containing the product
  10. customwere evaporated to dryness

Sources & evidence

ORD record
ord-301f99374cb745ffb020bd8a07d1f20e
Source dataset
uspto-grants-2001_08
Patent number
US06271234B1

Reaction notes

Loading…