Tributyltin Chloride → 3-((5-Bromo-2-methoxyphenyl)(tert-butyldimethylsilyloxy)methyl)-2,6-difluoro-5-(tributylstannyl)pyridine

HRID 335903Notes

Reaction equation

HRID 335903 reaction equation
[Li+].CCC[CH2-].[Br:6][C:7]1[CH:8]=[CH:9][C:10]([O:30][CH3:31])=[C:11]([CH:13]([O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])[C:14]2[C:15]([F:21])=[N:16][C:17]([F:20])=[CH:18][CH:19]=2)[CH:12]=1.[CH2:32]([Sn:36](Cl)([CH2:41][CH2:42][CH2:43][CH3:44])[CH2:37][CH2:38][CH2:39][CH3:40])[CH2:33][CH2:34][CH3:35]>C1COCC1>[Br:6][C:7]1[CH:8]=[CH:9][C:10]([O:30][CH3:31])=[C:11]([CH:13]([O:22][Si:23]([C:26]([CH3:27])([CH3:28])[CH3:29])([CH3:24])[CH3:25])[C:14]2[C:15]([F:21])=[N:16][C:17]([F:20])=[C:18]([Sn:36]([CH2:37][CH2:38][CH2:39][CH3:40])([CH2:41][CH2:42][CH2:43][CH3:44])[CH2:32][CH2:33][CH2:34][CH3:35])[CH:19]=2)[CH:12]=1

Participants

5

Reactant 3

HCID 15096Tributyltin ChlorideHCID 61028n-Butyl lithiumHCID 673831653-((5-Bromo-2-methoxyphenyl)(tert-butyldimethylsilyloxy)methyl)-2,6-difluoropyridine

Product 1

HCID 673829473-((5-Bromo-2-methoxyphenyl)(tert-butyldimethylsilyloxy)methyl)-2,6-difluoro-5-(tributylstannyl)pyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

DIPA (1.2 mL, 8.49 mmol) (freshly distilled) was dissolved in dry THF (40 mL) under nitrogen and cooled in a dry ice bath to −78°. N-butyllithium solution (2.5 m in hexanes, 3.0 mL, 7.50 mmol) was added and the solution stirred for a few minutes. A solution of 3-((5-bromo-2-methoxyphenyl)(tert-butyldimethylsilyloxy)methyl)-2,6-difluoropyridine (3.20 g, 7.20 mmol) in dry THF (20 mL) was added dropwise via an addition funnel and the solution stirred for 1 hour. Tributyltin chloride (2.0 mL, 7.37 mmol) was added to the pale yellow solution and it was stirred for 10 minutes. The reaction was quenched by addition of saturated ammonium chloride (10 mL). Water (100 mL) and diethyl ether (200 mL) were added and the phases mixed and separated. The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (2-15% diethyl ether in hexane gradient) gave 3-((5-bromo-2-methoxyphenyl)(tert-butyldimethylsilyloxy)methyl)-2,6-difluoro-5-(tributylstannyl)pyridine.

Workup

  1. distillationDIPA (1.2 mL, 8.49 mmol) (freshly distilled)
  2. dissolutionwas dissolved in dry THF (40 mL) under nitrogen
  3. temperaturecooled in a dry ice bath to −78°
  4. stirringthe solution stirred for 1 hour
  5. stirringwas stirred for 10 minutes
  6. customThe reaction was quenched by addition of saturated ammonium chloride (10 mL)
  7. additionWater (100 mL) and diethyl ether (200 mL) were added
  8. additionthe phases mixed
  9. customseparated
  10. dry with materialThe organic was dried with magnesium sulfate
  11. customevaporated to dryness under reduced pressure
  12. customPurification

Sources & evidence

ORD record
ord-8c6f987778b04b5a9ea89ea3b84e81b8
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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