Trifluoroacetic acid → HCID 69947711, compound

HRID 990987Notes

Reaction equation

HRID 990987 reaction equation
C([N-]C(C)C)(C)C.[Li+].[C:9]([O:13][C:14]([NH:16][N:17]=[C:18]1[C:26]2[C:21](=[CH:22][C:23]([O:27][CH3:28])=[CH:24][CH:25]=2)[CH2:20][CH2:19]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].[S:29]1[CH:33]=[CH:32][CH:31]=[C:30]1[C:34](OCC)=O.FC(F)(F)C(O)=O>CCCCCCC.C1COCC1.C(C1C=CC=CC=1)C.O1CCCC1.ClCCl>[CH3:28][O:27][C:23]1[CH:22]=[C:21]2[C:26](=[CH:25][CH:24]=1)[C:18]1[NH:17][N:16]([C:14]([O:13][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:15])[CH:34]([C:30]3[S:29][CH:33]=[CH:32][CH:31]=3)[C:19]=1[CH2:20]2

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 76052Ethyl 2-thenoateHCID 2724682Lithium diisopropylamideHCID 56980124HCID 56980124, compound

Product 1

HCID 69947711HCID 69947711, compound

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 22742125Tetrahydrofuran heptane ethylbenzolSolvent

Procedure

Lithium diisopropylamide (27.2 ml of a 2.0M solution in heptane/THF/ethylbenzene) was added dropwise to a stirred solution of 5-methoxyindan-1-one tert-butyloxycarbonylhydrazone (5.0 g) in tetrahydrofuran (150 ml) at −78° C. under nitrogen with stirring. After the addition was complete the mixture was stirred for 1.5 hours at −78° C. and then a solution of ethyl thiophen-2-carboxylate (3.39 g) in tetrahydrofuran (25 ml) was added dropwise. The mixture was stirred at −78° C. for 1.5 hours and then allowed to warm to ambient temperature. After 30 minutes the reaction mixture was quenched by the addition of saturated ammonium chloride solution and the layers were separated. The aqueous phase was extracted with ether. The combined organic phases were washed with 2M hydrochloric acid, dried, filtered and evaporated to give a residue which was dissolved in dichloromethane (100 ml) and trifluoroacetic acid (0.35 ml) was added. The mixture was stirred under a nitrogen atmosphere at ambient temperature and then purified by flash column chromatography using ethyl acetate/petroleum ether b.p 60-80° C. (4:1) as the mobile phase to give 6-methoxy-2-tert-butyloxycarbonyl-3-(2-thienyl)-1,4-dihydroindeno[1,2-c]pyrazole.

Workup

  1. additionAfter the addition
  2. stirringwas stirred for 1.5 hours at −78° C.
  3. stirringThe mixture was stirred at −78° C. for 1.5 hours
  4. customAfter 30 minutes the reaction mixture was quenched by the addition of saturated ammonium chloride solution
  5. customthe layers were separated
  6. extractionThe aqueous phase was extracted with ether
  7. washThe combined organic phases were washed with 2M hydrochloric acid
  8. customdried
  9. filtrationfiltered
  10. customevaporated
  11. customto give a residue which
  12. stirringThe mixture was stirred under a nitrogen atmosphere at ambient temperature
  13. custompurified by flash column chromatography
  14. customethyl acetate/petroleum ether b.p 60-80° C. (4:1)

Sources & evidence

ORD record
ord-8f1f26d57edf49d29c23c2939f1d2485
Source dataset
uspto-grants-2002_10
Patent number
US06462036B1

Reaction notes

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