Hydrochloric Acid → 1-(6-Bromo-3-fluoro-4-triethylsilanyl-pyridin-2-yl)-ethanone

HRID 1752454Notes

Reaction equation

HRID 1752454 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[Br:13][C:14]1[CH:19]=[C:18]([Si:20]([CH2:25][CH3:26])([CH2:23][CH3:24])[CH2:21][CH3:22])[C:17]([F:27])=[CH:16][N:15]=1.[Li+].CC([N-]C(C)C)C.[CH3:36][C:37](N(C)C)=[O:38].Cl>C1COCC1.[Cl-].[Na+].O.COC(C)(C)C.O>[Br:13][C:14]1[N:15]=[C:16]([C:37](=[O:38])[CH3:36])[C:17]([F:27])=[C:18]([Si:20]([CH2:25][CH3:26])([CH2:23][CH3:24])[CH2:21][CH3:22])[CH:19]=1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 31374DimethylacetamideHCID 2724682Lithium diisopropylamideHCID 866680682-Bromo-5-fluoro-4-(triethylsilyl)pyridineHCID 178418339Butyllithium

Product 1

HCID 866680691-(6-Bromo-3-fluoro-4-triethylsilanyl-pyridin-2-yl)-ethanoneYield 91%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 15413tert-Butyl methyl etherSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of diisopropylamine (25.4 g, 251 mmol) in THF (500 ml) was added n-BuLi (100 ml, 2.5 mol/L in hexanes) below −50° C. A solution of 2-bromo-5-fluoro-4-triethylsilanyl-pyridine (56.04 g, 193 mmol) in THF (60 ml) was added to the LDA-solution at −78° C. in a dropwise manner below −65° C. After 70 minutes at −78° C. DMA (23.51 ml, 251 mmol) was added dropwise in a fast manner to the deep red solution keeping the temperature below −57° C. After 15 minutes the cooling bath was removed and the reaction mixture was allowed to reach −40° C. The cold reaction mixture was poured on a mixture of 2M aq. HCl (250 ml)/water (200 ml)/brine (100 ml). Tert.-butyl methyl ether was added and the layers were separated. The organic phase was washed twice with brine, dried over magnesium sulfate, filtered and evaporated to give a yellow oil. The crude product (64.76 g) was chromatographed over silica gel (hexane/TBME) to give the title compound as a yellow liquid: 58.3 g (91% yield).

Workup

  1. customthe temperature below −57° C
  2. customAfter 15 minutes the cooling bath was removed
  3. customto reach −40° C
  4. customThe cold reaction mixture
  5. customthe layers were separated
  6. washThe organic phase was washed twice with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customto give a yellow oil
  11. customThe crude product (64.76 g) was chromatographed over silica gel (hexane/TBME)

Sources & evidence

ORD record
ord-6322e8efad5142d7b92be88265b6dd4d
Source dataset
uspto-grants-2015_10
Patent number
US09163011B2

Reaction notes

Loading…