Sulfuric Acid → Ethyl 7-(4-Cyclopentyl-3-(trifluoromethyl)benzyloxy)-3-(2-ethoxy-2-oxoethyl)-1,2,3,4-tetrahydrocyclopenta[b]indole-3-carboxylate

HRID 2040594Notes

Reaction equation

HRID 2040594 reaction equation
S(=O)(=O)(O)O.[CH2:6]([O:8][C:9](=[O:22])[CH2:10][C:11]1([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:15][CH2:14][CH2:13][C:12]1=O)[CH3:7].Cl.[CH:24]1([C:29]2[CH:44]=[CH:43][C:32]([CH2:33][O:34][C:35]3[CH:40]=[CH:39][C:38]([NH:41]N)=[CH:37][CH:36]=3)=[CH:31][C:30]=2[C:45]([F:48])([F:47])[F:46])[CH2:28][CH2:27][CH2:26][CH2:25]1>CCO>[CH:24]1([C:29]2[CH:44]=[CH:43][C:32]([CH2:33][O:34][C:35]3[CH:40]=[CH:39][C:38]4[NH:41][C:12]5[C:11]([CH2:10][C:9]([O:8][CH2:6][CH3:7])=[O:22])([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:15][CH2:14][C:13]=5[C:37]=4[CH:36]=3)=[CH:31][C:30]=2[C:45]([F:46])([F:47])[F:48])[CH2:25][CH2:26][CH2:27][CH2:28]1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 4418640Ethyl 1-(2-ethoxy-2-oxoethyl)-2-oxocyclopentanecarboxylateHCID 67211930(4-(4-Cyclopentyl-3-(trifluoromethyl)benzyloxy)phenyl)hydrazine Hydrochloride

Product 1

HCID 67220483Ethyl 7-(4-Cyclopentyl-3-(trifluoromethyl)benzyloxy)-3-(2-ethoxy-2-oxoethyl)-1,2,3,4-tetrahydrocyclopenta[b]indole-3-carboxylateYield 77.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

In a 1 L flask was placed EtOH (500 mL). Sulfuric acid (2.4 g, 23.98 mmol) was added at 40° C., followed by ethyl 1-(2-ethoxy-2-oxoethyl)-2-oxocyclopentanecarboxylate (15.2 g, 62.7 mmol). (4-(4-Cyclopentyl-3-(trifluoromethyl)benzyloxy)phenyl)hydrazine hydrochloride (24.0 g, 62.0 mmol) was added and the solution became light yellow and homogenous. The reaction mixture was refluxed overnight with a Dean-Starks condenser attached. The mixture was cooled and extracted in ethyl acetate (3×100 mL). The organics were washed with water (200 mL), sodium bicarbonate solution (2×70 mL), water (100 mL), dried over magnesium sulfate, and concentrated. The residue was dissolved in hexanes/ethyl acetate (80:20, 300 mL), added silica gel (30 g) and stirred for 35 minutes. The slurry was filtered, washed with the same elution solvent (100 mL) and the filtrate was concentrated to give the title compound (26.7 g). LCMS m/z=558.5 [M+H]+.

Workup

  1. customIn a 1 L flask was placed
  2. temperatureThe reaction mixture was refluxed overnight with a Dean-Starks condenser
  3. temperatureThe mixture was cooled
  4. extractionextracted in ethyl acetate (3×100 mL)
  5. washThe organics were washed with water (200 mL), sodium bicarbonate solution (2×70 mL), water (100 mL)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in hexanes/ethyl acetate (80:20, 300 mL)
  9. additionadded silica gel (30 g)
  10. filtrationThe slurry was filtered
  11. washwashed with the same elution solvent (100 mL)
  12. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-4be0ed5f6e014183a1460c450c6e0ee3
Source dataset
uspto-grants-2013_11
Patent number
US08580841B2

Reaction notes

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