Ethylene Glycol → 1-Acetyl-5,7,8,9-tetrahydrocyclohepta[f]indazol-6(1H)-one

HRID 718817Notes

Reaction equation

HRID 718817 reaction equation
[O:1]1CCO[C:2]21[CH2:21][C:10]1[CH:11]=[C:12]3[C:16](=[CH:17][C:9]=1[CH2:8][CH2:7][CH2:6]2)[N:15]([C:18](=[O:20])[CH3:19])[N:14]=[CH:13]3.C(O)CO.CC1C=CC(S(O)(=O)=O)=CC=1.[OH-].[K+]>C1(C)C=CC=CC=1>[C:18]([N:15]1[C:16]2[C:12](=[CH:11][C:10]3[CH2:21][C:2](=[O:1])[CH2:6][CH2:7][CH2:8][C:9]=3[CH:17]=2)[CH:13]=[N:14]1)(=[O:20])[CH3:19]

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 6101p-Toluenesulfonic acidHCID 14797Potassium HydroxideHCID 867224251-(5,7,8,9-Tetrahydro-1H-spiro[cyclohepta[f]indazole-6,2'-[1,3]dioxolan]-1-yl)ethanone

Product 1

HCID 867224261-Acetyl-5,7,8,9-tetrahydrocyclohepta[f]indazol-6(1H)-oneYield 94.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
142 °C

Procedure

1-Acetyl-5,7,8,9-tetrahydrocyclohepta[f]indazol-6(1H)-one (79) (30 g, 124 mmol) was added to a round bottom flask, equipped with a Dean Stark trap and condenser. Ethane-1,2-diol (27.6 mL, 495 mmol), pTSA (2.36 g, 12.38 mmol) and toluene (300 mL) were added and the resulting mixture was heated to about 142° C. for about 90 min. After cooling to rt, the mixture was concentrated and sonicated with water (˜50 mL). The resulting solids were collected by filtration and taken into MeOH (200 mL) and water (200 mL). Potassium hydroxide (13.9 g, 248 mmol) was added and the mixture was stirred at rt for about 30 min. The mixture was extracted with DCM (300 mL), washed with brine (200 mL), dried over MgSO4 and concentrated to afford 5,7,8,9-tetrahydro-M-spiro[cyclohepta[f]indazole-6,2′-[1,3]dioxolane] (81), (28.3 g, 93%); LC/MS, method 1, Rt=1.20 min, MS m/z 245 (M+H)+1H NMR (400 MHz, DMSO) δ 12.79 (bs, 1H), 7.93-7.87 (m, 1H), 7.44 (s, 1H), 7.22 (s, 1H), 3.97-3.76 (m, 4H), 3.06 (s, 2H), 2.91-2.81 (m, 2H), 1.91-1.81 (m, 2H), 1.70-1.59 (m, 2H).

Workup

  1. customequipped with a Dean Stark trap and condenser
  2. temperatureAfter cooling to rt
  3. concentrationthe mixture was concentrated
  4. customsonicated with water (˜50 mL)
  5. filtrationThe resulting solids were collected by filtration
  6. extractionThe mixture was extracted with DCM (300 mL)
  7. washwashed with brine (200 mL)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-50bd203af38f4570b9223689a0906f81
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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