HCID 68483642, compound → HCID 59438399, compound

HRID 2177502Notes

Reaction equation

HRID 2177502 reaction equation
[CH2:1]([Mg]Br)[CH3:2].[CH3:5][N:6]1[C:11](=O)[CH2:10][CH2:9][C:8]([NH:19][C:20](=[O:22])[OH:21])([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:7]1>CCOCC.C1COCC1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:8]([O:21][C:20](=[O:22])[NH:19][C:8]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:9][CH2:10][C:11]2([CH2:2][CH2:1]2)[N:6]([CH3:5])[CH2:7]1)([CH3:13])([CH3:9])[CH3:7]

Participants

6

Reactant 2

HCID 68483642HCID 68483642, compoundHCID 178418443HCID 178418443, compound

Product 1

HCID 59438399HCID 59438399, compoundYield 11%

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 333 ul (1.0 mmol) of a 3M ethyl magnesium bromide solution in ether in 4 ml THF was cooled to −70° C. A solution of 124 ul (0.42 mmol) titanium isopropoxide in 0.4 ml THF was added dropwise. The light brown mixture was stirred for 2 minutes. A solution of 122 mg (0.4 mmol) rac-(1-Methyl-6-oxo-3-phenyl-piperidin-3-yl)-carbamic acid ter!-butyl ester (example A.22, step 2) in 2.4 ml THF was added dropwise. The mixture was allowed to warm to room temperature and was stirred for 3 hours. The mixture was cooled in an ice bath and quenched with a 20% ammonium chloride solution. Water and ethyl acetate were added. The white suspension was filtered through a pad of dicalite. The organic layer was separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified on silica gel (Eluent: Heptane/ethyl acetate 0 to 100%) to provide 14 mg (11%) of the title compound as a colorless oil. MS (m/e): 317.2 (M+H).

Workup

  1. stirringwas stirred for 3 hours
  2. temperatureThe mixture was cooled in an ice bath
  3. customquenched with a 20% ammonium chloride solution
  4. additionWater and ethyl acetate were added
  5. filtrationThe white suspension was filtered through a pad of dicalite
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted twice with ethyl acetate
  8. dry with materialThe combined organic phases were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified on silica gel (Eluent: Heptane/ethyl acetate 0 to 100%)

Sources & evidence

ORD record
ord-7116701274a542dc8711663348997395
Source dataset
uspto-grants-2015_06
Patent number
US09067911B2

Reaction notes

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