Cesium fluoride → 2-Bromo-1-[3-(tert-butyl)-5-(4-hydroxypiperidino)-4-methoxyphenyl]-1-ethanone

HRID 1295963Notes

Reaction equation

HRID 1295963 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:17]([CH3:20])([CH3:19])[CH3:18])[C:5]([O:15][CH3:16])=[C:6]([N:8]2[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]2)[CH:7]=1.C([Sn](CCCC)(CCCC)[C:26]([O:28]CC)=[CH2:27])CCC.[F-].[Cs+].[Br:41]N1C(=O)CCC1=O>O1CCOCC1.CCOCC.O1CCCC1.O.C([O-])(O)=O.[Na+].C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:41][CH2:28][C:26]([C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]2)[C:5]([O:15][CH3:16])=[C:4]([C:17]([CH3:20])([CH3:19])[CH3:18])[CH:3]=1)=[O:27]

Participants

12

Reactant 4

HCID 25953Cesium fluorideHCID 67184N-bromobutanimideHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 589100191-[5-Bromo-3-(tert-butyl)-2-methoxyphenyl]-4-piperidinol

Product 1

HCID 589099592-Bromo-1-[3-(tert-butyl)-5-(4-hydroxypiperidino)-4-methoxyphenyl]-1-ethanoneYield 51.2%

Reagents, catalysts & solvents 7

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of the 1-[5-bromo-3-(tert-butyl)-2-methoxyphenyl]-4-piperidinol (1.3 g, 3.8 mmol), tributyl(1-ethoxyvinyl)tin (1.5 g, 4.2 mmol), tetrakis(triphenylphosphine)palladium (440 mg, 0.38 mmol) and CsF (1.27 g, 8.4 mmol) in 1,4-dioxane (8 ml) was stirred at 100° C. for 2.5 hours under a nitrogen stream. After completion of the reaction, the mixture was cooled to room temperature and diluted with Et2O, and the insoluble portion was filtered through celite. The solvent was distilled off under reduced pressure, the obtained crude product was dissolved in tetrahydrofuran (8 ml)-water (0.8 ml), N-bromosuccinimide (0.75 g, 4.2 mmol) was added while cooling on ice and the mixture was stirred at the same temperature for 15 minutes. This was diluted with a saturated NaHCO3 aqueous solution and ethyl acetate, and then the organic layer was separated and washed with brine. After drying with anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (solvent: n-hexane-ethyl acetate) to yield the title compound (748 mg, 51%) as a light yellow oil.

Workup

  1. customAfter completion of the reaction
  2. filtrationthe insoluble portion was filtered through celite
  3. distillationThe solvent was distilled off under reduced pressure
  4. customthe obtained crude product
  5. additionwas added
  6. temperaturewhile cooling on ice
  7. customthe organic layer was separated
  8. washwashed with brine
  9. dry with materialAfter drying with anhydrous magnesium sulfate
  10. distillationthe solvent was distilled off under reduced pressure
  11. customthe residue was purified by silica gel column chromatography (solvent: n-hexane-ethyl acetate)

Sources & evidence

ORD record
ord-5f8598e1bbb640d9b23cb4b029b7aa67
Source dataset
uspto-grants-2007_07
Patent number
US07244730B2

Reaction notes

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