Methyl iodide → (4S)-4-(3,4-dichlorophenyl)-2-methyl-3,4-dihydronaphthalen-1(2H)-one

HRID 556171Notes

Reaction equation

HRID 556171 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](=[O:19])[CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].[Li+].[CH3:21][Si]([N-][Si](C)(C)C)(C)C.[CH3:30]I.[CH2:32]1[CH2:36][O:35][CH2:34][CH2:33]1>>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]2[C:10]3[C:32](=[CH:33][CH:34]=[CH:30][CH:11]=3)[C:36](=[O:35])[C:13]([CH3:12])([CH3:14])[CH2:18]2)[CH:5]=[CH:6][C:7]=1[Cl:8].[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](=[O:19])[CH:11]([CH3:21])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 8028TetrahydrofuranHCID 1474501Sertraline ketoneHCID 2733832Lithium Hexamethyldisilazide

Product 2

HCID 58950780(4S)-4-(3,4-dichlorophenyl)-2-methyl-3,4-dihydronaphthalen-1(2H)-oneYield 60%HCID 66809033(S)-4-(3,4-dichlorophenyl)-2,2-dimethyl-3,4-dihydronaphthalen-1(2H)-oneYield 15%

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-4-(3,4-dichlorophenyl)-3,4-dihydronaphthalen-1(2H)-one (1) (2.0 g, 6.89 mmol) in THF (50 mL) at −78° C. was added LiHMDS (1.0 M in THF, 8.27 mL, 8.27 mmol). The reaction mixture was stirred for 20 min at −78° C. before MeI (1.17 g, 0.52 mL, 8.27 mmol) was added. The reaction mixture was stirred and warmed to 0° C. over 2 h before being quenched by a saturated solution of NH4Cl (20 mL). The product was extracted with ethyl acetate (100 mL ×2), dried and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=1:7 to 1:5) to give (S)-4-(3,4-dichlorophenyl)-2,2-dimethyl-3,4-dihydronaphthalen-1(2H)-one (56) (0.33 g, 15%) and (4S)-4-(3,4-dichlorophenyl)-2-methyl-3,4-dihydronaphthalen-1 (2H)-one (55) (1.25 g, 60%).

Workup

  1. additionwas added
  2. custombefore being quenched by a saturated solution of NH4Cl (20 mL)
  3. extractionThe product was extracted with ethyl acetate (100 mL ×2)
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane=1:7 to 1:5)

Sources & evidence

ORD record
ord-c216c9f2a96f4d2d92f5ab54473dd073
Source dataset
uspto-grants-2011_11
Patent number
US08053603B2

Reaction notes

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