Tetrahydrofuran → 2-(tert-Butyldimethylsilyloxymethyl)-5-(1-hydroxy-3-methyl-butyl)-pyridine

HRID 2041574Notes

Reaction equation

HRID 2041574 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:8][O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])=[N:6][CH:7]=1.[Li][CH2:18]CCC.[Cl-].[NH4+].[CH2:24]1[CH2:28][O:27][CH2:26][CH2:25]1>>[Si:10]([O:9][CH2:8][C:5]1[CH:4]=[CH:3][C:2]([CH:28]([OH:27])[CH2:24][CH:25]([CH3:18])[CH3:26])=[CH:7][N:6]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 116594545-Bromo-2-({[t-butyl(dimethyl)silyl]oxy}methyl)pyridineHCID 178418339Butyllithium

Product 1

HCID 576565292-(tert-Butyldimethylsilyloxymethyl)-5-(1-hydroxy-3-methyl-butyl)-pyridineYield 64%

Conditions

Temperature
-78 °C

Procedure

Dissolve 5-bromo-2-(tert-butyldimethylsilyloxymethyl)-pyridine (0.5 g, 1.654 mmol, prepared by following the procedure described in J. Med. Chem. 1987, 30, 871-880) in anhydrous THF (12 mL). Cool the solution to −78° C., add n-BuLi (1.14 mL, 1.819 mmol, 1.6M solution in hexane) and stir at this temperature for 40 min. Add slowly isovaleryl aldehyde (0.284 mL, 2.646 mmol) and stir the mixture for 5 h at −78° C. Add additional isovaleryl aldehyde (0.089 mL, 0.827 mmol) and stir the mixture for 1.5 h at −78° C. Add ammonium chloride at −78° C. and warm the mixture to room temperature. Add EtOAc 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 (4:1) to give the desired intermediate as oil (330 mg, 64%). GC-MS m/z: 309 (M+).

Workup

  1. customprepared
  2. stirringstir the mixture for 5 h at −78° C
  3. stirringstir the mixture for 1.5 h at −78° C
  4. extractionAdd EtOAc 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 (4:1)

Sources & evidence

ORD record
ord-4124387d094644caa70217af14a88f84
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

Loading…