Triethylamine → 3-[(3,6-dihydro-4-phenyl-1(2H)-pyridinyl)methyl]cyclohexanone

HRID 1034195Notes

Reaction equation

HRID 1034195 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH2:8][CH:7]([C:11](O)=O)[CH2:6]2)OCC1.C(N(CC)CC)C.ClC(OCC(C)C)=O.[C:29]1([C:35]2[CH2:36][CH2:37][NH:38][CH2:39][CH:40]=2)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>ClCCl>[C:29]1([C:35]2[CH2:40][CH2:39][N:38]([CH2:11][CH:7]3[CH2:8][CH2:9][CH2:10][C:5](=[O:1])[CH2:6]3)[CH2:37][CH:36]=2)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 825531,2,3,6-Tetrahydro-4-phenylpyridineHCID 5674921,4-Dioxaspiro[4.5]decane-7-carboxylic acid

Product 1

HCID 117778783-[(3,6-dihydro-4-phenyl-1(2H)-pyridinyl)methyl]cyclohexanoneYield 74.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 1,4-dioxaspiro[4.5]decane-7-carboxylic acid (Step A) (99.3 g) and triethylamine (80.8 g) in 1000 mL of dichloromethane is cooled in an ice bath, and treated dropwise with isobutyl chloroformate (80.1 g), dropwise, under nitrogen. After 30 minutes, a solution of 4-phenyl-1,2,3,6-tetrahydropyridine (84.7 g) in 500 mL of dichloromethane is added dropwise over a 2-hour period. The mixture is stirred at room temperature for 2 additional hours. The solvent is removed in vacuo. The residue is suspended in 1000 mL of ethyl acetate, cooled to 0° C., and sequentially washed with ice-cold 1N aqueous hydrochloric acid solution and brine, dried over magnesium sulfate, and evaporated in vacuo. The crude product is purified by flash chromatography (silica; hexane:ethyl acetate, 3:1) to give 107.1 g of the title compound as a yellow oil (silica; Rf =0.4; 1% methanol, 99% chloroform); Mass Spectrum (Electron Ionization) (MS (EI)) 327 (M, 26.1%), 141 (100%).

Workup

  1. customThe solvent is removed in vacuo
  2. temperaturecooled to 0° C.
  3. washsequentially washed with ice-cold 1N aqueous hydrochloric acid solution and brine
  4. dry with materialdried over magnesium sulfate
  5. customevaporated in vacuo
  6. customThe crude product is purified by flash chromatography (silica; hexane:ethyl acetate, 3:1)

Sources & evidence

ORD record
ord-32492e9303084ec0a450824771820a30
Source dataset
uspto-grants-1994_05
Patent number
US05314896

Reaction notes

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