Methyl 4-(3-mercaptophenyl)-3,4,5,6-tetrahydro-2H-pyran-4-carboxylate → Ethyl 4-[3-[4-(2-methylimidazol-1-yl)phenylthio]phenyl]-3,4,5,6-tetrahydro-2H-pyran-4-carboxylate

HRID 1418464Notes

Reaction equation

HRID 1418464 reaction equation
[SH:1][C:2]1[CH:3]=[C:4]([C:8]2([C:14]([O:16][CH3:17])=[O:15])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[CH3:18][C:19]1[N:20]([C:24]2[CH:29]=[CH:28][C:27](I)=[CH:26][CH:25]=2)[CH:21]=[CH:22][N:23]=1.[CH3:31]C(C)([O-])C.[Na+]>C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:18][C:19]1[N:20]([C:24]2[CH:29]=[CH:28][C:27]([S:1][C:2]3[CH:3]=[C:4]([C:8]4([C:14]([O:16][CH2:17][CH3:31])=[O:15])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]4)[CH:5]=[CH:6][CH:7]=3)=[CH:26][CH:25]=2)[CH:21]=[CH:22][N:23]=1

Participants

6

Reactant 3

HCID 11242202Methyl 4-(3-mercaptophenyl)-3,4,5,6-tetrahydro-2H-pyran-4-carboxylateHCID 112890901-(4-iodophenyl)-2-methyl-1H-imidazoleHCID 23676156Sodium t-butoxide

Product 1

HCID 11154431Ethyl 4-[3-[4-(2-methylimidazol-1-yl)phenylthio]phenyl]-3,4,5,6-tetrahydro-2H-pyran-4-carboxylateYield 60.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Procedure

A solution of methyl 4-(3-mercaptophenyl)-3,4,5,6-tetrahydro-2H-pyran-4-carboxylate (1.04 g, 3.5 mmol), 4-(2-methylimidazol-1-yl)phenyliodide (0.89 g, 3.5 mmol), sodium t-butoxide (673 mg, 7 mmol) and tetrakis(triphenylphosphine)palladium (162 mg, 0.14 mmol) in dry ethanol (20 ml) was heated to reflux with stirring overnight. Volatiles were removed by evaporation and the residue was partitioned between ethyl acetate (100 ml) and water (100 ml). The aqueous layer was extracted with ethyl acetate (100 ml). The combined organic layers were washed with brine (100 ml), dried (magnesium sulfate) and concentrated to dryness to give 1.09 g of crude product as a brown liquid. Purification by column chromatography (silica-gel, 50 g; methanol in dichloromethane, increasing the ratio of methanol from 0% to 4%) afforded the titled compound (0.90 g).

Workup

  1. temperatureto reflux
  2. customVolatiles were removed by evaporation
  3. customthe residue was partitioned between ethyl acetate (100 ml) and water (100 ml)
  4. extractionThe aqueous layer was extracted with ethyl acetate (100 ml)
  5. washThe combined organic layers were washed with brine (100 ml)
  6. dry with materialdried (magnesium sulfate)
  7. concentrationconcentrated to dryness
  8. customto give 1.09 g of crude product as a brown liquid
  9. customPurification by column chromatography (silica-gel, 50 g
  10. temperaturemethanol in dichloromethane, increasing the ratio of methanol from 0% to 4%)

Sources & evidence

ORD record
ord-647197e07ebc4ea8949b7604123b93af
Source dataset
uspto-grants-1999_03
Patent number
US05883106

Reaction notes

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