Pyridine → HCID 66596945, compound

HRID 1518624Notes

Reaction equation

HRID 1518624 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]1.[O:9]=[C:10](Cl)OC(Cl)(Cl)Cl.S(C1C=CC(C)=CC=1)(O)(=O)=O.[NH2:28][C:29]1[CH:30]=[C:31]([CH2:41][CH2:42][CH2:43][C:44]([O:46][CH2:47][C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)=[O:45])[CH:32]=[CH:33][C:34]=1[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.N1C=CC=CC=1>C(#N)C.O.CN(C)C=O>[CH3:8][N:5]1[CH2:6][CH2:7][CH:2]([O:1][C:10]([NH:28][C:29]2[CH:30]=[C:31]([CH2:41][CH2:42][CH2:43][C:44]([O:46][CH2:47][C:48]3[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=3)=[O:45])[CH:32]=[CH:33][C:34]=2[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)=[O:9])[CH2:3][CH2:4]1

Participants

8

Reactant 4

HCID 1049PyridineHCID 10426DiphosgeneHCID 660484-Piperidinol, 1-methyl-HCID 87066192HCID 87066192, compound

Product 1

HCID 66596945HCID 66596945, compoundYield 88.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

Under a nitrogen flow, 4-hydroxy-1-methylpiperidine (10.4 g, 90.0 mmol) was dissolved in acetonitrile (100 mL) and to the solution was added, under ice-water cooling, a solution of diphosgene (35.6 g, 180 mmol) in acetonirile (50 mL) After stirring at room temperature for 5 hours, the reaction mixture was concentrated under reduced pressure to obtain a solid. The solid obtained was added to a solution of benzyl 4-(3-amino-4-phenylphenyl)butyrate tosylate (31.1 g, 60.0 mmol) in a mixed solvent of pyridine (50 mL) and N,N-dimethylformamide (150 mL), and the mixture was stirred at room temperature for 2 hours. Under ice-water cooling, the reaction was stopped by addition of purified water and the reaction mixture was extracted with ethyl acetate. The organic layer was washed with a dilute aqueous solution of sodium hydroxide and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by flash column chromatography to obtain benzyl 4-[3-({[(1-methylpiperidin-4-yl)oxy]carbonyl}amino)-4-phenylphenyl]butyrate (25.8 g).

Workup

  1. additionwas added, under ice-water cooling
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. customto obtain a solid
  4. customThe solid obtained
  5. extractionthe reaction mixture was extracted with ethyl acetate
  6. washThe organic layer was washed with a dilute aqueous solution of sodium hydroxide
  7. dry with materiala saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-5608eadba88248f88e548aa739044d5e
Source dataset
uspto-grants-2015_07
Patent number
US09072734B2

Reaction notes

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