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

HRID 538362Notes

Reaction equation

HRID 538362 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.CN(C)[C:30](=[O:32])[CH3:31].Cl>C1COCC1.[Cl-].[Na+].O.O>[Br:13][C:14]1[N:15]=[C:16]([C:30](=[O:32])[CH3:31])[C:17]([F:27])=[C:18]([Si:20]([CH2:25][CH3:26])([CH2:23][CH3:24])[CH2:21][CH3:22])[CH:19]=1

Participants

9

Reactant 5

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

Product 1

HCID 866680691-(6-Bromo-3-fluoro-4-triethylsilanyl-pyridin-2-yl)-ethanoneYield 91.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-40 °C

Procedure

A solution of diisopropylamine (25.4 g, 250 mmol) in 500 ml THF was cooled to −75° C. BuLi (100 ml, 250 mmol, 2.5 M in hexanes) was added dropwise while maintaining the temperature below −50° C. After the reaction temperature had reached −75° C. again, a solution of 2-bromo-5-fluoro-4-triethylsilanyl-pyridine (56.04 g, 193 mmol) in 60 ml THF was added dropwise. The mixture was stirred in a dry ice bath for 70 minutes. N,N-dimethylacetamide (21.87 g, 250 mmol) was added quickly, the reaction temperature rose to −57° C. The reaction mixture was stirred in a dry ice bath for 15 min and then allowed to warm to −40° C. It was poured on a mixture of 2M aq. HCl (250 ml, 500 mmol), 250 ml water and 100 ml brine. The mixture was extracted with TBME, washed with brine, dried over MgSO4.H2O, filtered and evaporated to give a yellow oil which was purified on a silica gel column by eluting with hexane/0-5% TBME to yield 58.5 g of the title compound as a yellow liquid. TLC (Hex/TBME 99/1): Rf=0.25; HPLC: RtH11=1.921 min; ESIMS: 332, 334 [(M+H)+, 1Br]; 1H-NMR (400 MHz, CDCl3): 7.57 (d, 1H), 2.68 (s, 3H), 1.00-0.84 (m, 15H).

Workup

  1. temperaturewhile maintaining the temperature below −50° C
  2. customhad reached −75° C.
  3. customrose to −57° C
  4. stirringThe reaction mixture was stirred in a dry ice bath for 15 min
  5. extractionThe mixture was extracted with TBME
  6. washwashed with brine
  7. dry with materialdried over MgSO4.H2O
  8. filtrationfiltered
  9. customevaporated
  10. customto give a yellow oil which
  11. customwas purified on a silica gel column
  12. washby eluting with hexane/0-5% TBME

Sources & evidence

ORD record
ord-0942b5d013924490b48f5e406b89ba46
Source dataset
uspto-grants-2014_10
Patent number
US08865712B2

Reaction notes

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