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

HRID 1644025
Notes
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Reaction equation

HRID 1644025 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]
ParticipantsProcedureWorkupSources & evidenceReaction notes

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 8028
Tetrahydrofuran
Solvent

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-4246d234c1c843d3b0e6064afece05e0
Source dataset
uspto-grants-2012_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08124121B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes