Methyl iodide → 2-Methyl-4-(4-t-butyldimethylsiloxybutyl)-epsilon-caprolactone

HRID 465564Notes

Reaction equation

HRID 465564 reaction equation
[CH:1](NC(C)C)(C)C.C([Li])CCC.[Si:13]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH:25]1[CH2:32][CH2:31][O:30][C:28](=[O:29])[CH2:27][CH2:26]1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].CI>O1CCCC1.CCCCCC>[CH3:1][CH:27]1[CH2:26][CH:25]([CH2:24][CH2:23][CH2:22][CH2:21][O:20][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])[CH2:32][CH2:31][O:30][C:28]1=[O:29]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 99720434-(4-t-Butyldimethylsiloxybutyl)-epsilon-caprolactoneHCID 178418339Butyllithium

Product 1

HCID 100413622-Methyl-4-(4-t-butyldimethylsiloxybutyl)-epsilon-caprolactone

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

To a solution of 14.3 ml (0.1 mole) of diisopropylamine in 170 ml dry tetrahydrofuran is added dropwise 37 ml (93 mmol) of a 2.5M solution of n-butyllithium in hexane. The solution is stirred for 15 min and then a solution of 13.86 g (46.1 mmol) of 4-(4-t-butyldimethylsilyloxybutyl)-epsilon-caprolactone in 68 ml dry tetrahydrofuran is added slowly. The yellow solution is stirred at room temperature for 0.5 h and 19 ml (0.3 mole) methyl iodide is added rapidly. The exothermic reaction is controlled by cooling in a water bath. The reaction mixture is stirred for 3 h and quenched using saturated aqueous ammonium chloride solution. The mixture is extracted with ether and the organic layer is washed with water and brine. The organic phase is dried, filtered, concentrated and purified by chromatography using 3:2 hexane/ether as eluent to yield 2-methyl-4-(4-t-butyldimethylsilyloxybutyl)-epsilon-caprolactone; NMR (CDCl3): delta 4-4.4 (m,2H), 3.6 (t,2H), 1.2 (d,3H), 0.88 (s,9H). This is converted to methyl 8-amino-2-methyl-4-[3-(3-pyridyl)propyl]-octanoate in a similar fashion as described below for the 2,2-dimethyl analog.

Workup

  1. stirringThe yellow solution is stirred at room temperature for 0.5 h
  2. customThe exothermic reaction
  3. temperatureby cooling in a water bath
  4. stirringThe reaction mixture is stirred for 3 h
  5. customquenched
  6. extractionThe mixture is extracted with ether
  7. washthe organic layer is washed with water and brine
  8. customThe organic phase is dried
  9. filtrationfiltered
  10. concentrationconcentrated
  11. custompurified by chromatography

Sources & evidence

ORD record
ord-b131ca23804649dd9b810b15a9da736c
Source dataset
uspto-grants-1992_10
Patent number
US05153214

Reaction notes

Loading…