Triethylamine → HCID 66889511, compound

HRID 253234Notes

Reaction equation

HRID 253234 reaction equation
O[CH2:2][C:3]1[CH:4]=[CH:5][C:6]([O:24][CH3:25])=[C:7]([O:9][CH2:10][CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)[CH:8]=1.[CH2:26]([N:28](CC)CC)C.CS(Cl)(=O)=O.[C-]#N.[K+]>ClCCl.O.CN(C=O)C>[C:26]([CH2:2][C:3]1[CH:4]=[CH:5][C:6]([O:24][CH3:25])=[C:7]([O:9][CH2:10][CH:11]2[CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:22])([CH3:23])[CH3:21])=[O:18])[CH2:15][CH2:16]2)[CH:8]=1)#[N:28]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 9032Potassium CyanideHCID 31297Methanesulfonyl chlorideHCID 66889504HCID 66889504, compound

Product 1

HCID 66889511HCID 66889511, compoundYield 41%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1,1-dimethylethyl 4-({[5-(hydroxymethyl)-2-(methyloxy) phenyl]oxy}methyl)piperidine-1-carboxylate (1.88 g, 5.4 mmol) in dichloromethane (14 mL) was added triethylamine (2.3 mL, 16.2 mmol). The resulting mixture was cooled with an ice bath, and methanesulfonyl chloride (0.84 mL, 10.8 mmol) was added dropwise. The mixture was allowed to warm to room temperature and a white precipitate formed. After 2.5 h, the solvent was removed and the residue was dissolved in water, which was subsequently extracted twice with ethyl acetate. The organic layers were combined, dried over sodium sulfate, filtered, and concentrated to provide a yellow oil. To the oil was added DMF (10 mL) and potassium cyanide (703 mg, 10.8 mmol). The resulting mixture was stirred at rt for 15 h. Water was then added, and the aqueous mixture was extracted twice with ethyl acetate. The organic layers were combined, washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography (60% hexanes, 40% ethyl acetate) to provide 800 mg of 1,1-dimethylethyl 4-({[5-(cyanomethyl)-2-(methyloxy)phenyl]oxy}methyl)piperidine-1-carboxylate (2.2 mmol, 41% yield). 1H NMR (400 MHz, CDCl3): δ6.89-6.81 (m, 3H), 4.15 (br m, 2H), 3.86 (s, 3H), 3.86-3.83 (m, 2H), 3.69 (s, 2H), 2.76 (br m, 2H), 2.10-2.00 (m, 1H), 1.87 (br d, 2H), 1.47 (s, 9H), 1.31-1.20 (m, 2H); MS (EI) for C20H28N2O4: 383 (MNa+).

Workup

  1. temperatureThe resulting mixture was cooled with an ice bath
  2. customa white precipitate formed
  3. customthe solvent was removed
  4. dissolutionthe residue was dissolved in water
  5. extractionwhich was subsequently extracted twice with ethyl acetate
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto provide a yellow oil
  10. extractionthe aqueous mixture was extracted twice with ethyl acetate
  11. washwashed with brine
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe residue was purified by flash chromatography (60% hexanes, 40% ethyl acetate)

Sources & evidence

ORD record
ord-d995a06f8157428eab1ffef8427a2bd4
Source dataset
uspto-grants-2011_01
Patent number
US07872014B2

Reaction notes

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