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

HRID 1295963노트

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HRID 1295963 반응식
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]

참가 물질

12

반응물 4

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

생성물 1

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

시약·촉매·용매 7

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매HCID 516892Sodium Bicarbonate용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-5f8598e1bbb640d9b23cb4b029b7aa67
출처 데이터셋
uspto-grants-2007_07
특허 번호
US07244730B2

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