Sodium bis(trimethylsilyl)amide → (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-(1-methyl-1H-pyrazol-4-yl)piperidin-2-one

HRID 1048329Notes

Reaction equation

HRID 1048329 reaction equation
[CH2:1]([C@@:4]1([CH3:25])[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[NH:6][C:5]1=[O:24])[CH:2]=[CH2:3].[CH3:26][N:27]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[N:28]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>CN(C)C1C=CN=CC=1.C1(C)C=CC=CC=1.C(O[Cu]OC(=O)C)(=O)C>[CH2:1]([C@@:4]1([CH3:25])[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:6]([C:30]2[CH:29]=[N:28][N:27]([CH3:26])[CH:31]=2)[C:5]1=[O:24])[CH:2]=[CH2:3]

Participants

7

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 58574008(3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methylpiperidin-2-one

Product 1

HCID 67999210(3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-(1-methyl-1H-pyrazol-4-yl)piperidin-2-one

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 178476681HCID 178476681, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
115 °C

Procedure

(3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methylpiperidin-2-one (Example 71, Step D) (90 mg, 0.24 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (125 mg, 0.60 mmol), diacetoxycopper (44 mg, 0.24 mmol) and N,N-dimethylpyridin-4-amine (88 mg, 0.72 mmol) were dissolved in 1.2 mL of toluene. Sodium bis(trimethylsilyl)amide (480 μL, 0.48 mmol) was added and the reaction apparatus was outfitted with a reflux condenser and was allowed to stir at 115° C. for 13 hours. The reaction mixture was cooled to room temperature, quenched with water and extracted (2×EtOAc). The combined organic layers were washed with sat. aq. NaCl solution, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. Purification of the residue by flash chromatography (0 to 60% EtOAc/hexanes) provided the title compound as a colorless solid.

Workup

  1. customthe reaction apparatus was outfitted with a reflux condenser
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customquenched with water
  4. extractionextracted (2×EtOAc)
  5. washThe combined organic layers were washed with sat. aq. NaCl solution
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customPurification of the residue by flash chromatography (0 to 60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-9a04a5209e9a4731920b238897190392
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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