Sulfuric Acid → 2-{2-Methoxymethyl-4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy)-2-methylpropionic acid ethyl ester

HRID 898486Notes

Reaction equation

HRID 898486 reaction equation
[CH2:1]([O:3][C:4](=[O:32])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:11][C:10]=1[CH2:30][OH:31])([CH3:7])[CH3:6])[CH3:2].[CH3:33]I.[H-].[Na+].S(=O)(=O)(O)O>CN(C=O)C.[Cl-].[Na+].O.CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:32])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:11][C:10]=1[CH2:30][O:31][CH3:33])([CH3:7])[CH3:6])[CH3:2]

Participants

8

Reactant 4

HCID 1118Sulfuric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 235900112-{2-Hydroxymethyl-4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy)-2-methylpropionic acid ethyl ester

Product 1

HCID 589790592-{2-Methoxymethyl-4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy)-2-methylpropionic acid ethyl esterYield 51%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a 15 mL round bottom flask under a nitrogen atmosphere were charged 0.075 g (0.17 mmol) of 2-{2-hydroxymethyl-4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy}-2-methylpropionic acid ethyl ester, dissolved in 1 mL of anhydrous DMF, followed by the addition of 0.16 mL (1.7 mmol) of methyl iodide. The reaction solution was cooled down in an ice bath and was treated with 0.014 g (0.34 mmol) of NaH. The reaction was stirred cold for 2 h. Next the reaction was poured into 6 mL of EtOAc and 10 mL of brine, and then acidified using dilute sulfuric acid. The organic layer was separated away, dried over Na2SO4, and removed in vacuo to give a crude oil. This crude residue was purified using radial chromatography with a 1 mm normal phase silica gel plate, eluting with 15:85 EtOAc:Hex to give a colorless oil (0.039 g, 51%). MS (ES) m/e 454 (M+1).

Workup

  1. temperatureThe reaction solution was cooled down in an ice bath
  2. customThe organic layer was separated away
  3. dry with materialdried over Na2SO4
  4. customremoved in vacuo
  5. customto give a crude oil
  6. customThis crude residue was purified
  7. washeluting with 15:85 EtOAc

Sources & evidence

ORD record
ord-eba74881127b4731b306845931ad8909
Source dataset
uspto-grants-2008_04
Patent number
US07351728B2

Reaction notes

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