Trifluoroacetic acid → HCID 69947711, compound

HRID 1280793Notes

Reaction equation

HRID 1280793 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.[Cl-].[NH4+].CC1C(C)=C(C)C(C)=C(C)C=1.FC(F)(F)C(O)=O>CCCCCCC.C1COCC1.C(C1C=CC=CC=1)C.O1CCCC1.ClCCl.CCOCC>[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

11

Reactant 6

HCID 6422Trifluoroacetic acidHCID 12784PentamethylbenzeneHCID 25517Ammonium ChlorideHCID 76052Ethyl 2-thenoateHCID 2724682Lithium diisopropylamideHCID 56980124HCID 56980124, compound

Product 1

HCID 69947711HCID 69947711, compound

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 22742125Tetrahydrofuran heptane ethylbenzolSolvent

Procedure

A solution of lithium diisopropylamide (11.3 ml of a 20M solution in heptane/THF/ethylbenzene) was added dropwise to a stirred solution of 5-methoxyindan-1-one tert-butyloxycarbonylhydrazone (2.5 g) in tetrahydrofuran (100 ml) at −78° C. under nitrogen. The mixture was stirred at this temperature for 1.5 hours and then a solution of ethyl thiophene-2-carboxylate (1.69 g) in tetrahydrofuran (10 ml) was added dropwise. After the addition the mixture was stirred for 30 minutes at −78° C. and then allowed to warm to ambient temperature. After stirring for a further 20 minutes at ambient temperature, saturated ammonium chloride solution (100 ml) was added and the mixture was stirred vigorously for ten minutes. The layers were separated and the aqueous layer was extracted with ether (3×75 ml). The combined organics were washed with 1M hydrochloric acid, then brine, and then dried, filtered and evaporated to give a yellow gum which was suspended in dichloromethane (25 ml) and pentamethylbenzene (1.34 g) was added. The mixture was cooled to 0° C. and trifluoroacetic acid (0.2 ml) was added. The mixture was stirred for 64 hours and then concentrated under reduced pressure to give an oil which was dissolved in ether (200 ml), washed with saturated sodium bicarbonate solution (100 ml), then brine, then dried, filtered and evaporated to give a gum which was purified by flash column chromatography using petroleum ether, b.p. 60-80° C./ethyl acetate (4:1) as the mobile phase to give 6-methoxy-2-tert-butyloxycarbonyl-3-(2-thienyl)-1,4-dihydroindeno[1,2-c]pyrazole, m.p. 163-165° C.

Workup

  1. additionAfter the addition the mixture
  2. stirringwas stirred for 30 minutes at −78° C.
  3. stirringAfter stirring for a further 20 minutes at ambient temperature
  4. stirringthe mixture was stirred vigorously for ten minutes
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with ether (3×75 ml)
  7. washThe combined organics were washed with 1M hydrochloric acid
  8. dry with materialbrine, and then dried
  9. filtrationfiltered
  10. customevaporated
  11. customto give a yellow gum which
  12. temperatureThe mixture was cooled to 0° C.
  13. stirringThe mixture was stirred for 64 hours
  14. concentrationconcentrated under reduced pressure
  15. customto give an oil which
  16. washwashed with saturated sodium bicarbonate solution (100 ml)
  17. dry with materialbrine, then dried
  18. filtrationfiltered
  19. customevaporated
  20. customto give a gum which
  21. customwas purified by flash column chromatography

Sources & evidence

ORD record
ord-89f5944133d14fccb371eee1d1ce9cf3
Source dataset
uspto-grants-2002_09
Patent number
US06451834B1

Reaction notes

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