Pyridine → Ethyl 5-methyl-4-oxo-2,3,7,8-tetrahydro-4H-1-benzothiopyran-6-carboxylate

HRID 1597656

반응식

HRID 1597656 반응식
[CH3:1][C:2]1[CH:3]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:4][CH2:5][C:6](=O)[CH:7]=1.[SH:14][CH2:15][CH2:16][C:17](O)=[O:18].C1(C)C=CC(S(O)(=O)=O)=CC=1.N1C=CC=CC=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O.CS(O)(=O)=O>C1(C)C=CC=CC=1>[CH3:1][C:2]1[C:7]2[C:17](=[O:18])[CH2:16][CH2:15][S:14][C:6]=2[CH2:5][CH2:4][C:3]=1[C:9]([O:11][CH2:12][CH3:13])=[O:10]

참가 물질

8

반응물 6

HCID 1049PyridineHCID 6101p-Toluenesulfonic acidHCID 6395Methanesulfonic AcidHCID 65143-Mercaptopropionic AcidHCID 9845Trifluoroacetic anhydrideHCID 790204-Carbethoxy-3-methyl-2-cyclohexen-1-one

생성물 1

HCID 10868786Ethyl 5-methyl-4-oxo-2,3,7,8-tetrahydro-4H-1-benzothiopyran-6-carboxylate수율 36%

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

A mixture of ethyl 2-methyl-4-oxo-2-cyclohexenecarboxylate (2.0 kg, 91.2%, 10.98 moles), β-mercaptopropionic acid (1.165 kg, 10.98 moles), p-toluenesulfonic acid (ptsa) monchydrate (0.710 kg, 3.73 moles) and pyridine (0.304 kg, 3.84 moles) in toluene is heated to reflux temperature, heated at reflux temperatures for 7 hours using a Dean Stark trap for removal of water, allowed to cool to room temperature over a 17 hour period, cooled to 50° C., treated with trifluoroacetic anhydride (TFAA) (2.306 kg, 10.98 moles) at 50°-12° C., treated with methanesulfonic acid (0.053 kg, 0.55 moles), allowed to warm to room temperature, held at room temperature until reaction is complete by HPLC analysis and quenched with water. The phases are separated. The organic phase is washed with water and distilled to remove the toluene. The remaining pot residue is treated with isopropyl alcohol (1.89 kg), cooled to 45° C., treated with heptane (1.65 kg), and cooled to room temperature. The resultant mixture is filtered and the filtercake is washed sequentially with a 1:1 isopropanol:heptane mixture (0.735 kg) and heptane (1.37 kg). The washed filtercake is dried in vacuo to give he title product as a white crystalline solid, 0.931 kg (36% yield) 98.4% purity, identified by HPLC analysis.

후처리

  1. temperatureis heated
  2. temperatureto reflux temperature
  3. temperatureheated
  4. temperatureat reflux temperatures for 7 hours
  5. customfor removal of water
  6. temperaturecooled to 50° C.
  7. temperatureto warm to room temperature
  8. customheld at room temperature until reaction
  9. customquenched with water
  10. customThe phases are separated
  11. washThe organic phase is washed with water
  12. distillationdistilled
  13. customto remove the toluene
  14. additionThe remaining pot residue is treated with isopropyl alcohol (1.89 kg)
  15. temperaturecooled to 45° C.
  16. additiontreated with heptane (1.65 kg)
  17. temperaturecooled to room temperature
  18. filtrationThe resultant mixture is filtered
  19. washthe filtercake is washed sequentially with a 1:1 isopropanol
  20. customThe washed filtercake is dried in vacuo

출처 및 근거

ORD 기록
ord-fc80103c497a46eb986b4193eabe54f8
출처 데이터셋
uspto-grants-2001_09
특허 번호
US06294676B2

연결된 노트

불러오는 중…