Iodine → 5-((Tert-butyldimethylsilyl)oxy)-1-(2,4-difluoro-5-(pyrimidin-5-yl)phenyl)-2-methylenepentan-1-one

HRID 1907424Notes

Reaction equation

HRID 1907424 reaction equation
Br[C:2](=[CH2:14])[CH2:3][CH2:4][CH2:5][O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8].[Mg].II.[F:18][C:19]1[CH:26]=[C:25]([F:27])[C:24]([C:28]2[CH:29]=[N:30][CH:31]=[N:32][CH:33]=2)=[CH:23][C:20]=1[CH:21]=[O:22]>C1COCC1.O>[Si:7]([O:6][CH2:5][CH2:4][CH2:3][C:2](=[CH2:14])[C:21]([C:20]1[CH:23]=[C:24]([C:28]2[CH:33]=[N:32][CH:31]=[N:30][CH:29]=2)[C:25]([F:27])=[CH:26][C:19]=1[F:18])=[O:22])([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]

Participants

7

Reactant 4

HCID 807Iodine2×HCID 5462224MagnesiumHCID 156000924-Bromo-4-pentenyl tert-butyl(dimethyl)silyl etherHCID 866853452,4-Difluoro-5-(pyrimidin-5-yl)benzaldehyde

Product 1

HCID 866853465-((Tert-butyldimethylsilyl)oxy)-1-(2,4-difluoro-5-(pyrimidin-5-yl)phenyl)-2-methylenepentan-1-oneYield 24.99%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of ((4-bromopent-4-en-1-yl)oxy)(tert-butyl)dimethylsilane (prepared following the procedures of Rostami, Organic Letters, 2007), 9(4), 703-706) (3.30 g, 11.81 mmol) in THF (25 mL) was added to a flask filled with magnesium (0.574 g, 23.62 mmol) and iodine (0.092 g, 0.363 mmol), and the resulting dark brown suspension was stirred at rt for 15 min and then heated under reflux for 45 min. The color changed from brown to deep reddish and the color of iodine faded 10 min under reflux. Eventually, the color of the reaction mixture turned to grey. This regent was cooled to rt and then added to a suspension of 2,4-difluoro-5-(pyrimidin-5-yl)benzaldehyde (Preparation 15, 2 g, 9.08 mmol) in THF (14 mL), and the reaction mixture was stirred at rt for 12 h. Water was added and the aqueous layer was extracted with EtOAc (×3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and filtered, and the filtrate was evaporated in vacuo to give the crude product. The crude product was purified by silica gel chromatography eluting with 0-35% EtOAc/Hexane to give 5-((tert-butyldimethylsilyl)oxy)-1-(2,4-difluoro-5-(pyrimidin-5-yl)phenyl)-2-methylenepentan-1-one (0.95 g, 2.270 mmol, 24.99% yield). 1H NMR (500 MHz, CHLOROFORM-d) δ 9.27 (s, 1H), 8.93 (d, J=1.4 Hz, 2H), 7.59 (dd, J=8.2, 7.3 Hz, 1H), 7.20-7.03 (m, 1H), 6.04 (s, 1H), 5.78 (d, J=1.8 Hz, 1H), 3.70 (t, J=6.3 Hz, 2H), 2.62-2.41 (m, 2H), 1.85-1.70 (m, 2H), 0.93 (m, 9H), 0.09 (m, 6H).

Workup

  1. additionwas added to a flask
  2. temperatureheated
  3. temperatureunder reflux for 45 min
  4. temperatureunder reflux
  5. temperatureThis regent was cooled to rt
  6. stirringthe reaction mixture was stirred at rt for 12 h
  7. extractionthe aqueous layer was extracted with EtOAc (×3)
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. customthe filtrate was evaporated in vacuo
  12. customto give the crude product
  13. customThe crude product was purified by silica gel chromatography
  14. washeluting with 0-35% EtOAc/Hexane

Sources & evidence

ORD record
ord-f02bb6ac596f4b99b5cee6e429690c53
Source dataset
uspto-grants-2013_12
Patent number
US08598161B2

Reaction notes

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