Acetone → HCID 68670243, compound

HRID 2071074Notes

Reaction equation

HRID 2071074 reaction equation
[Li]CCCC.Br[C:7]1[CH:8]=[N:9][CH:10]=[C:11]([CH2:13][O:14][Si:15]([CH:22]([CH3:24])[CH3:23])([CH:19]([CH3:21])[CH3:20])[CH:16]([CH3:18])[CH3:17])[CH:12]=1.[CH3:25][C:26]([CH3:28])=[O:27]>C1(C)C=CC=CC=1>[CH:16]([Si:15]([CH:22]([CH3:24])[CH3:23])([CH:19]([CH3:21])[CH3:20])[O:14][CH2:13][C:11]1[CH:12]=[C:7]([C:26]([OH:27])([CH3:28])[CH3:25])[CH:8]=[N:9][CH:10]=1)([CH3:18])[CH3:17]

Participants

5

Reactant 3

HCID 180AcetoneHCID 121095753-Bromo-5-((triisopropylsilyloxy)methyl)pyridineHCID 178418339Butyllithium

Product 1

HCID 68670243HCID 68670243, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Procedure

Toluene (30 mL) in a 3-necked flask was cooled down to −78° C. n-BuLi (1.6 M in hexane, 8.35 mL, 0.13.35 mmol) was slowly added to the toluene. After 10 minutes a solution of the 3-bromo-5-((triisopropylsilyloxy)methyl)pyridine (4.0 g, 11.62 mmol) in toluene (30 mL) was added dropwise. A yellow solid precipitated. The resulting slurry was aged for 15-30 min, then THF (20 mL) was added slowly, keeping the internal temperature at <−50° C. The mixture was aged for 15 min, then acetone (1.7 mL, 23.24 mmol) was added over 2 min. The solids dissolved and a brown homogeneous solution was obtained. The reaction solution was warmed to rt and quenched with saturated aqueous NH4Cl and diluted with EtOAc. The phases were separated and aqueous layer was extracted with EtOAc twice. The organic layers were combined and concentrated to dryness. Purification by flash chromatography (silica gel, hexanes/EtOAc) gave 2-(5-((triisopropylsilyloxy)methyl)pyridin-3-yl)propan-2-ol as a light yellow solid (3.56 g, 96%). 1H NMR (CDCl3): d: 1.250-1.055 (m, 21H), 1.606 (s, 6H), 4.865 (s, 2H), 7.830 (s, 1H), 8.458 (s, 1H), 8.621 (s, 1H).

Workup

  1. customA yellow solid precipitated
  2. additionTHF (20 mL) was added slowly
  3. customat <−50° C
  4. waitThe mixture was aged for 15 min
  5. dissolutionThe solids dissolved
  6. customa brown homogeneous solution was obtained
  7. customquenched with saturated aqueous NH4Cl
  8. additiondiluted with EtOAc
  9. customThe phases were separated
  10. extractionaqueous layer was extracted with EtOAc twice
  11. concentrationconcentrated to dryness
  12. customPurification by flash chromatography (silica gel, hexanes/EtOAc)

Sources & evidence

ORD record
ord-67681a0249224bfe8d5d3bd1dd90e005
Source dataset
uspto-grants-2012_10
Patent number
US08299267B2

Reaction notes

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