2,2-Dimethoxypropane → (3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-3-methylpiperidin-2-one

HRID 932006Notes

Reaction equation

HRID 932006 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[NH:12][C:11](=[O:21])[C@:10]([CH2:23][CH:24]([OH:27])[CH2:25][OH:26])([CH3:22])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.CO[C:30](OC)([CH3:32])[CH3:31].CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[NH:12][C:11](=[O:21])[C@:10]([CH2:23][CH:24]3[CH2:25][O:26][C:30]([CH3:32])([CH3:31])[O:27]3)([CH3:22])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 64952,2-DimethoxypropaneHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 58573319(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-(2,3-dihydroxypropyl)-3-methylpiperidin-2-one

Product 1

HCID 58573060(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-3-methylpiperidin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-(2,3-dihydroxypropyl)-3-methylpiperidin-2-one (Example 102, Step A) (4.900 g, 12.00 mmol) and 2,2-dimethoxypropane (14.76 mL, 120 mmol) in N,N-dimethylformamide (34 mL) at room temperature was added CSA (0.279 g, 1.200 mmol) and the reaction mixture was allowed to stir for 1 hr at room temperature. The reaction was quenched with sodium bicarbonate (100 mL) and EtOAc (100 mL). The layers were separated and the organic layer was washed three times with sat. sodium carbonate (100 mL). The aqueous layers were combined and were extracted with EtOAc (200 mL). The organic layers were combined, washed with sat. aq. NaCl solution, dried with sodium sulfate, filtered, and concentrated under reduced pressure to provide the title compound.

Workup

  1. customThe reaction was quenched with sodium bicarbonate (100 mL) and EtOAc (100 mL)
  2. customThe layers were separated
  3. washthe organic layer was washed three times with sat. sodium carbonate (100 mL)
  4. extractionwere extracted with EtOAc (200 mL)
  5. washwashed with sat. aq. NaCl solution
  6. dry with materialdried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f11852a8e6554dd1b6cb022c0d484c36
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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