Methyl iodide → HCID 86612787, compound

HRID 2364450Notes

Reaction equation

HRID 2364450 reaction equation
[CH2:1]([O:3][CH:4]([O:18][CH2:19][CH3:20])[CH2:5][CH2:6][NH:7][C:8](=[O:17])[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:2].[Li+].[CH3:22][Si]([N-][Si](C)(C)C)(C)C.CI>CN(C=O)C>[CH2:1]([O:3][CH:4]([O:18][CH2:19][CH3:20])[CH2:5][CH2:6][N:7]([CH3:22])[C:8](=[O:17])[O:9][CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 53419200HCID 53419200, compound

Product 1

HCID 86612787HCID 86612787, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of phenylmethyl [3,3-bis(ethyloxy)propyl]carbamate (4.17 g, 14.8 mmol, J. Med. Chem. 1998 41, 3919-3922) in anhydrous DMF (15 mL) under nitrogen at ambient temperature was treated LiHMDS (1.0 M in THF, 17.8 mL, 17.8 mmol). After stirring 5 min., methyl iodide (1.11 mL, 17.8 mmol) was added. After stirring an additional 15 min., the reaction mixture was quenched by addition of saturated brine, water and Et2O. After separation of the phases, the aqueous layer was back-extracted with Et2O. The combined organic phases were washed with brine, dried over anhydrous MgSO4, filtered, evaporated in vacuo and purified on silica gel eluting with 25% EtOAc in Hexanes to provide the product as an oil: 1H NMR (CDCl3) δ 7.28-7.38 (5H, m), 5.12 (2H, s), 4.45-4.56 (1H, m), 3.29-3.68 (6H, m), 2.92 (3H, s), 1.81-1.90 (2H, m), 1.11-1.23 (6H, m); ES+ MS: 318 (M+Na+).

Workup

  1. stirringAfter stirring an additional 15 min.
  2. customthe reaction mixture was quenched by addition of saturated brine, water and Et2O
  3. customAfter separation of the phases
  4. extractionthe aqueous layer was back-extracted with Et2O
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. custompurified on silica gel eluting with 25% EtOAc in Hexanes

Sources & evidence

ORD record
ord-5d3f10e2b2b5456a987bd01b0a40389d
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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