Tetrahydrofuran → 5-(tert-Butyldimethylsilyloxymethyl)-2-(3-methyl-butyryl)-pyridine

HRID 2041578Notes

Reaction equation

HRID 2041578 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])=[CH:4][N:3]=1.[Li][CH2:18]CCC.[CH2:22]1[CH2:26][O:25][CH2:24][CH2:23]1>>[Si:10]([O:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([C:26](=[O:25])[CH2:22][CH:23]([CH3:18])[CH3:24])=[N:3][CH:4]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 6425754Pyridine, 2-bromo-5-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-HCID 178418339Butyllithium

Product 1

HCID 576559115-(tert-Butyldimethylsilyloxymethyl)-2-(3-methyl-butyryl)-pyridineYield 44%

Conditions

Temperature
-78 °C

Procedure

Dissolve 2-bromo-5-(tert-butyldimethylsilyloxymethyl)pyridine (1.99 g, 6.583 mmol, prepared by following the procedure described in J. Org. Chem. 2004, 69, 250-262) in anhydrous THF (20 mL). Cool the solution to −78° C., add n-BuLi (4.32 mL, 6.912 mmol, 1.6M solution in hexane) and stir at this temperature for 40 min. Add slowly a solution of N-methoxy-AT-methyl-3-methyl-butyramide (0.955 g, 6.583 mmol) in anhydrous THF (5 mL). Stir the mixture for 2 h at −78° C. and then allow the mixture to warm to room temperature. Add brine and extract the aqueous layer twice with EtOAc. Dry the combined organic extracts over Na2SO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting with hexane and hexane/EtOAc (19:1) to give the desired intermediate as yellow oil (890 mg, 44%). GC-MS m/z: 307 (M+).

Workup

  1. customprepared
  2. stirringStir the mixture for 2 h at −78° C.
  3. temperatureto warm to room temperature
  4. extractionAdd brine and extract the aqueous layer twice with EtOAc
  5. dry with materialDry the combined organic extracts over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customPurify the crude mixture by chromatography on silica gel eluting with hexane and hexane/EtOAc (19:1)

Sources & evidence

ORD record
ord-ef2c3eada0a64e8b85620a241605e1c5
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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