Sodium Iodide → Methyl-4-({4-[2-(benzyloxy)phenyl]-1,3-thiazol-2-yl}methyl)benzoate

HRID 1257467Notes

Reaction equation

HRID 1257467 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15]1[N:16]=[C:17]([CH2:20]O)[S:18][CH:19]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[I-].[Na+].[CH3:36][O:37][C:38]([C:40]1[CH:45]=[CH:44][C:43](B(O)O)=[CH:42][CH:41]=1)=[O:39].C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.CC(C)=O.COCCOC.C(O)C.O>[CH3:36][O:37][C:38](=[O:39])[C:40]1[CH:45]=[CH:44][C:43]([CH2:20][C:17]2[S:18][CH:19]=[C:15]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[N:16]=2)=[CH:42][CH:41]=1

Participants

11

Reactant 6

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 31297Methanesulfonyl chlorideHCID 27343694-Methoxycarbonylphenylboronic acidHCID 58127962{4-[2-(Benzyloxy)phenyl]-1,3-thiazol-2-yl}methanol

Product 1

HCID 58127863Methyl-4-({4-[2-(benzyloxy)phenyl]-1,3-thiazol-2-yl}methyl)benzoateYield 21.7%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 20074477Dimethoxyethane ethanolSolvent

Procedure

To a solution (8 mL) of the compound (1.2 g, 4.0 mmol) obtained in Example 191a in tetrahydrofuran were added triethylamine (0.73 mL, 5.3 mmol) and methanesulfonylchloride (0.38 mL, 4.8 mmol), and the mixture was stirred at room temperature for 3 hr. The resulting salt was filtered and removed, and the solvent was evaporated under reduced pressure. To a solution (40 mL) of the residue in acetone was added sodium iodide (1.8 g, 12 mmol), and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, the mixture was extracted with ethyl acetate, and the solvent was evaporated under reduced pressure. To a mixed solution of the residue, 4-methoxycarbonylphenylboronic acid (870 mg, 4.8 mmol) and 2M aqueous sodium carbonate solution (2.4 mL, 4.8 mmol) in 1,2-dimethoxyethane/ethanol (v/v=3/1, 12 mL) was added [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (330 mg, 0.40 mmol), and the mixture was stirred at 90° C. overnight. The resulting salt was filtered and removed, and the solvent was evaporated under reduced pressure. The obtained crude product was purified by column chromatography (hexane-hexane/ethyl acetate=85/15) to give the title compound (360 mg, 21% in 3 steps) as colorless crystals.

Workup

  1. filtrationThe resulting salt was filtered
  2. customremoved
  3. customthe solvent was evaporated under reduced pressure
  4. stirringthe mixture was stirred at room temperature overnight
  5. extractionthe mixture was extracted with ethyl acetate
  6. customthe solvent was evaporated under reduced pressure
  7. stirringthe mixture was stirred at 90° C. overnight
  8. filtrationThe resulting salt was filtered
  9. customremoved
  10. customthe solvent was evaporated under reduced pressure
  11. customThe obtained crude product
  12. customwas purified by column chromatography (hexane-hexane/ethyl acetate=85/15)

Sources & evidence

ORD record
ord-43d33fb47d9b4f9a84517ecfd7cf0239
Source dataset
uspto-grants-2013_06
Patent number
US08461348B2

Reaction notes

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