Methyl iodide → (R)-2-(1-methoxy-4-methylpentan-2-yl)isoindoline-1,3-dione

HRID 339319Notes

Reaction equation

HRID 339319 reaction equation
[OH:1][CH2:2][C@H:3]([N:8]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:18])[CH2:4][CH:5]([CH3:7])[CH3:6].[CH3:19]N(C)P(N(C)C)(N(C)C)=O.[H-].[Na+].IC>C1COCC1>[CH3:19][O:1][CH2:2][C@H:3]([N:8]1[C:9](=[O:18])[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:16]1=[O:17])[CH2:4][CH:5]([CH3:7])[CH3:6]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 12679HexamethylphosphoramideHCID 24758Sodium hydrideHCID 66772663(R)-2-(1-hydroxy-4-methylpentan-2-yl)isoindoline-1,3-dione

Product 1

HCID 66772667(R)-2-(1-methoxy-4-methylpentan-2-yl)isoindoline-1,3-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(R)-2-(1-hydroxy-4-methylpentan-2-yl)isoindoline-1,3-dione (example 9c) (5.88 g, 23.87 mmol) was dissolved in dry THF (25 mL) and hexamethyl-phosphoramide (30 mL) and the solution cooled to 0° C. Sodium hydride (60% in mineral oil, 1.15 g, 28.65 mmol) was added and after 10 minutes iodomethane (7.43 ml, 119.35 mmol) was added dropwise and the solution was warmed up slowly to room temperature and stirred over night. The reaction mixture was poured into ice/water, extracted with EtOAC, washed with brine, dried over MgSO4, filtered and evaporated. The residue was purified on silica gel (20% EtOAC in hexane) to give 3.92 g of (R)-2-(1-methoxy-4-methylpentan-2-yl)isoindoine-1,3-dione (63%).

Workup

  1. additionwas added dropwise
  2. extractionextracted with EtOAC
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified on silica gel (20% EtOAC in hexane)
  8. customto give 3.92 g of (R)-2-(1-methoxy-4-methylpentan-2-yl)isoindoine-1,3-dione (63%)

Sources & evidence

ORD record
ord-fac07dfd3f4e4d358623c766a1bff3fe
Source dataset
uspto-grants-2014_11
Patent number
US08895050B2

Reaction notes

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