Dimethyl Sulfoxide → HCID 86722345, compound

HRID 718768Notes

Reaction equation

HRID 718768 reaction equation
CS(C)=O.[H-].[Na+].[I-].[CH3:8][S+](C)(C)=O.FC1C=CC([N:20]2[C:28]3[C:23](=[CH:24][C:25]4[C@@:33]5([CH2:39]C6C=CC=CN=6)[CH2:34]CC(=O)C[C@H]5CCCC=4C=3)[CH:22]=[N:21]2)=CC=1.FC1C=CC(N2C3C(=CC4[C@:66]5([CH2:72][C:73]6C=CC=CN=6)[CH2:67][CH2:68][C:69](=[O:71])[CH2:70][C@@H:65]5[CH2:64][CH2:63]CC=4C=3)C=N2)=CC=1>C1COCC1.CCOC(C)=O>[CH2:72]([C:66]12[CH2:67][CH2:68][C:69]3([CH2:8][O:71]3)[CH2:70][CH:65]1[CH2:64][CH2:63][CH2:39][C:33]1[C:25]2=[CH:24][C:23]2[CH:28]=[N:20][NH:21][C:22]=2[CH:34]=1)[CH3:73]

Participants

7

Reactant 4

HCID 679Dimethyl Sulfoxide2×HCID 24758Sodium hydride2×HCID 74498Sulfoxonium, trimethyl-, iodide (1:1)2×HCID 131734185HCID 131734185, compound

Product 1

HCID 86722345HCID 86722345, compoundYield 139.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of DMSO (1 mL) and sodium hydride (60 wt % in oil, 0.020 g, 0.51 mmol) was heated to about 65° C. for about 45 min then cooled to rt and diluted with THF (1 mL). The mixture was cooled to about 0° C. and trimethylsulfoxonium iodide (0.112 g, 0.509 mmol) was added. The mixture was stirred for about 15 min and (4aS,12bR)-9-acetyl-12b-ethyl-1,2,4a,5,6,7,9,12b-octahydro-4H-9,10-diaza-benzo[3,4]cyclohepta[1,2-f]inden-3-one; compound with (4aR,12bS)-9-Acetyl-12b-ethyl-1,2,4a,5,6,7,9,12b-octahydro-4H-9,10-diaza-benzo[3,4]cyclohepta[1,2-f]inden-3-one (10, R1=Acetyl, R2=Ethyl) (0.066 g, 0.203 mmol) dissolved in THF (1.5 mL) was added. The mixture was warmed to rt and stirred for about 14 h. In a separate flask a mixture of DMSO (1 mL) and sodium hydride (60 wt % in oil, 0.020 g, 0.51 mmol) was heated to about 65° C. for about 45 min then cooled to rt and diluted with THF (0.5 mL). The mixture was cooled to about 0° C., trimethylsulfoxonium iodide (0.112 g, 0.51 mmol) was added and the mixture was stirred for about 15 min. The mixture was added to the epoxidation reaction and stirring was continued for about 2 h at rt. The reaction mixture was diluted with EtOAc (25 mL) and washed successively with sat. aq. NH4Cl (15 mL), water (15 mL), and brine (15 mL). The organic solution was died over MgSO4, filtered and concentrated under reduced pressure to provide crude rac-(2′R,4aS,12bR)-12b-ethyl-2,4,4a,5,6,7,9,12b-octahydro-1H-spiro[benzo[6,7]cyclohepta[1,2-f]indazole-3,2′-oxirane] (12, R1═H, R2=Ethyl) (0.084 g); LC/MS, method 3, Rt=2.32 min, MS m/z 297 (M+H)+. The material was used directly in Step #13 without further purification

Workup

  1. temperaturethen cooled to rt
  2. temperatureThe mixture was cooled to about 0° C.
  3. additionwas added
  4. temperatureThe mixture was warmed to rt
  5. stirringstirred for about 14 h
  6. temperaturewas heated to about 65° C. for about 45 min
  7. temperaturethen cooled to rt
  8. temperatureThe mixture was cooled to about 0° C.
  9. stirringthe mixture was stirred for about 15 min
  10. additionThe mixture was added to the epoxidation reaction
  11. stirringstirring
  12. waitwas continued for about 2 h at rt
  13. washwashed successively with sat. aq. NH4Cl (15 mL), water (15 mL), and brine (15 mL)
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-890b5e5e31034e8aa21dc44207da2f64
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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