2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → 2-Methylsulfanyl-thieno[2,3-h]quinazoline-8-carboxylic acid tert-butyl ester

HRID 643734Notes

Reaction equation

HRID 643734 reaction equation
[C:1]([O:5][C:6]([C:8]1[S:22][C:11]2[CH2:12][CH2:13][C:14]3[CH:15]=[N:16][C:17]([S:20][CH3:21])=[N:18][C:19]=3[C:10]=2[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(C1C(=O)C(Cl)=C(Cl)C(=O)C=1C#N)#N>O1CCOCC1.CC(C)=O>[C:1]([O:5][C:6]([C:8]1[S:22][C:11]2=[CH:12][CH:13]=[C:14]3[C:19]([N:18]=[C:17]([S:20][CH3:21])[N:16]=[CH:15]3)=[C:10]2[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinone2×HCID 592627552-Methylsulfanyl-5,6-dihydro-thieno[2,3-h]quinazoline-8-carboxylic acid tert-butyl ester

Product 1

HCID 592627012-Methylsulfanyl-thieno[2,3-h]quinazoline-8-carboxylic acid tert-butyl esterYield 73%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 312751,4-DioxaneSolvent

Procedure

2-Methylsulfanyl-5,6-dihydro-thieno[2,3-h]quinazoline-8-carboxylic acid tert-butyl ester (9.0 g, 26.91 mmol) and DDQ (12.22 g, 53.82 mmol) were suspended/dissolved in dry dioxane (100 mL) and heated at reflux for 1 hour. Further DDQ (12.22 g, 53.82 mmol) was added and the resulting suspension was heated at reflux for 1.5 hours. After cooling to room temperature the mixture was concentrated under reduced pressure and then partitioned between EtOAc and saturated Na2CO3. The aqueous layer was further extracted with EtOAc (3×200 mL) and the combined organics were washed with saturated Na2CO3 (2×250 mL) and brine (1×200 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The deep brown gum obtained was redissolved in hot acetone, silica (˜60 mL) was added and the resultant suspension was concentrated under reduced pressure. The solid obtained was subjected to column chromatography (gradient elution, 20-30% acetone in hexanes, ˜600 mL silica) giving a light brown solid (6.50 g, 73% yield). ). MS (ES+) 333. δH (CDCl3) 1.7 (9H, s), 2.8 (3H, s), 7.8 (1H, d), 7.9 (1H, d), 8.8 (1H, s), 9.2 (1H, s)

Workup

  1. temperatureheated
  2. temperatureat reflux for 1 hour
  3. temperaturethe resulting suspension was heated
  4. temperatureat reflux for 1.5 hours
  5. concentrationwas concentrated under reduced pressure
  6. custompartitioned between EtOAc and saturated Na2CO3
  7. extractionThe aqueous layer was further extracted with EtOAc (3×200 mL)
  8. washthe combined organics were washed with saturated Na2CO3 (2×250 mL) and brine (1×200 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe deep brown gum obtained
  13. additionsilica (˜60 mL) was added
  14. concentrationthe resultant suspension was concentrated under reduced pressure
  15. customThe solid obtained
  16. washwas subjected to column chromatography (gradient elution, 20-30% acetone in hexanes, ˜600 mL silica)

Sources & evidence

ORD record
ord-81ba9bfac3804e919499ce5e19b72a3d
Source dataset
uspto-grants-2010_04
Patent number
US07700609B2

Reaction notes

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