Iodine → Ethyl 2-iodo-5-(4-methoxyphenyl)oxazole-4-carboxylate

HRID 1410456Notes

Reaction equation

HRID 1410456 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:13][CH:12]=[N:11][C:10]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:5][CH:4]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[I:29]I.S([O-])([O-])(=O)=S.[Na+].[Na+]>C1COCC1.CCOC(C)=O>[I:29][C:12]1[O:13][C:9]([C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)=[C:10]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[N:11]=1

Participants

7

Reactant 4

HCID 807IodineHCID 24477Sodium ThiosulfateHCID 2733832Lithium HexamethyldisilazideHCID 2739749Ethyl 5-(4-methoxyphenyl)-1,3-oxazole-4-carboxylate

Product 1

HCID 68518841Ethyl 2-iodo-5-(4-methoxyphenyl)oxazole-4-carboxylateYield 80.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of ethyl 5-(4-methoxyphenyl)oxazole-4-carboxylate (2.75 g, 11.1 mmol) in anhydrous THF (20 mL) under an N2 atmosphere at −78° C. was added 1M lithium bis(trimethylsilyl)amide in THF (18 mL, 18 mmol), dropwise. The reaction mixture was stirred at −78° C. for one hour. A solution of iodine (5.0 g, 19.7 mmol) in anhydrous THF (10 mL) was added dropwise and the reaction stirred at −78° C. for a further 1 hour. The mixture was then warmed to −10° C. and 10% sodium thiosulfate solution and EtOAc was added. The aqueous phase was extracted with EtOAc and the combined organic phase was washed with brine, dried over MgSO4 and the solvent removed in vacuo. The residue was purified by silica gel column chromatography using a 10-40% EtOAc in hexanes gradient to afford ethyl 2-iodo-5-(4-methoxyphenyl)oxazole-4-carboxylate (3.33 g, 8.9 mmol, 80%) as a white solid. 1H NMR (CDCl3) 1.40 (3H, t), 3.87 (3H, s), 4.41 (2H, q), 6.98 (2H, d), 8.01 (2H, d). LCMS (1) Rt: 2.13 min; m/z (ES+) 374.

Workup

  1. stirringthe reaction stirred at −78° C. for a further 1 hour
  2. temperatureThe mixture was then warmed to −10° C.
  3. extractionThe aqueous phase was extracted with EtOAc
  4. washthe combined organic phase was washed with brine
  5. dry with materialdried over MgSO4
  6. customthe solvent removed in vacuo
  7. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-1f28ba8778ab40ad8f987c025d2f9572
Source dataset
uspto-grants-2014_12
Patent number
US08921544B2

Reaction notes

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