Methyl vinyl ketone → HCID 57603342, compound

HRID 1788094Notes

Reaction equation

HRID 1788094 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH:7]([CH2:12][CH2:13][F:14])[C:8]2=[O:11])=[CH:4][C:3]=1[O:15][CH3:16].C=C[C@@H]1[C@@H]2[CH2:25][C@H:26]([C@@H:27]([OH:38])[C:28]3C4C(=CC=CC=4)N=CC=3)[N+](CC3C=CC(C(F)(F)F)=CC=3)(CC2)C1.[Br-].C(C(C)=O)=C.[OH-].[K+]>C1(C)C=CC=CC=1.ClCCl>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7]([CH2:12][CH2:13][F:14])([CH2:25][CH2:26][C:27](=[O:38])[CH3:28])[C:8]2=[O:11])=[CH:4][C:3]=1[O:15][CH3:16]

Participants

7

Reactant 4

HCID 6570Methyl vinyl ketoneHCID 14797Potassium HydroxideHCID 11421253HCID 11421253, compoundHCID 57603291HCID 57603291, compound

Product 1

HCID 57603342HCID 57603342, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-chloro-2-(2-fluoroethyl)-5-methoxyindan-1-one (34 g, 140 mmol) in toluene (1500 mL) was added N-[4-(trifluoromethyl)benzyl]cinchoninium bromide (13 g, 24 mmol) and the mixture was stirred at room temperature for 30 minutes. After cooling to 0° C., methyl vinyl ketone (20 mL, 240 mmol) was added followed by potassium hydroxide pellets (85%, 34 g, ˜52 mmol) and the mixture was vigorously stirred for 90 minutes. The reaction mixture was diluted with dichloromethane (1000 mL), dried with MgSO4 and filtered. The filtrate was filtered through a pad of silica gel, washing with Et2O and EtOAc. The filtrate was concentrated under reduced pressure and the residue was chromatographed on silica gel (elution with 30% to 50% EtOAc/hexanes) to give 6-chloro-2-(2-fluoroethyl)-5-methoxy-2-(3-oxobutyl)indan-1-one as a yellow oil. Analysis by chiral HPLC indicated an enantiomeric ratio of approximately 2:1 favoring the desired (2S)-enantiomer. This enantiomerically enriched material was utilized for the remainder of the synthesis.

Workup

  1. temperatureAfter cooling to 0° C.
  2. stirringthe mixture was vigorously stirred for 90 minutes
  3. dry with materialdried with MgSO4
  4. filtrationfiltered
  5. filtrationThe filtrate was filtered through a pad of silica gel
  6. washwashing with Et2O and EtOAc
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe residue was chromatographed on silica gel (elution with 30% to 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-a422c20f5fe84af7b5f05ec4d1685d87
Source dataset
uspto-grants-2009_03
Patent number
US07511152B2

Reaction notes

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