Chlorotrimethylsilane → 2-bromo-1-(4-fluoro-5-methoxy-1-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3-dihydro-1H-inden-1-yl)ethanone

HRID 452560Notes

Reaction equation

HRID 452560 reaction equation
[F:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][C:6]2([C:24](=[O:26])[CH3:25])[CH2:13][C:14]1[CH:15]=[N:16][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:19]=1.Cl[Si](C)(C)C.[Br-:32].[Br-].[Br-].C1([N+](C)(C)C)C=CC=CC=1.C1([N+](C)(C)C)C=CC=CC=1.C1([N+](C)(C)C)C=CC=CC=1>C1COCC1>[Br:32][CH2:25][C:24]([C:6]1([CH2:13][C:14]2[CH:15]=[N:16][C:17]([C:20]([F:22])([F:23])[F:21])=[CH:18][CH:19]=2)[C:7]2[C:3](=[C:2]([F:1])[C:10]([O:11][CH3:12])=[CH:9][CH:8]=2)[CH2:4][CH2:5]1)=[O:26]

Participants

5

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 17977687Phenyltrimethylammonium bromide dibromideHCID 669235341-(4-fluoro-5-methoxy-1-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3-dihydro-1H-inden-1-yl)ethanone

Product 1

HCID 866508482-bromo-1-(4-fluoro-5-methoxy-1-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3-dihydro-1H-inden-1-yl)ethanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

1-(4-fluoro-5-methoxy-1-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3-dihydro-1H-inden-1-yl)ethanone (600 mg, 1.6 mmol) was diluted in THF (3 ml). This solution was cooled to −78° C. and Sodium bis(hexamethylsilyl) amide (1.8 ml, 1.8 mmol) was added. After stirring for 10 min, chloro trimethylsilane (230 μl, 1.8 mmol) was added drop wise at −78° C., after which the reaction was warmed to 0° C., and left stirring for 30 min. To this solution was added Phenyltrimethylammonium tribromide (680 mg, 1.8 mmol) portion wise, and THF (1 mL) was added for solubility purposes. The reaction mixture was allowed to warm to room temp. Aqueous work up, extracted with dichloromethane, dried over magnesium sulfate, filtered, concentrated under reduced pressure furnished 2-bromo-1-(4-fluoro-5-methoxy-1-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3-dihydro-1H-inden-1-yl)ethanone. Used without further purification.

Workup

  1. temperatureafter which the reaction was warmed to 0° C.
  2. waitleft
  3. stirringstirring for 30 min
  4. temperatureto warm to room temp
  5. extractionAqueous work up, extracted with dichloromethane
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c4e9f792eaf9460f947e7829531bd227
Source dataset
uspto-grants-2013_07
Patent number
US08492387B2

Reaction notes

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