Toluene → HCID 9806979, compound

HRID 2182773Notes

Reaction equation

HRID 2182773 reaction equation
[CH:1]1([C:6]2[C:15]([CH:16]([F:27])[C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=3)=[C:14]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[C:13]3[C:12](=[O:35])[CH2:11][C:10]([CH3:37])([CH3:36])[CH2:9][C:8]=3[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C[Li].[Cl-].[NH4+].[C:42]1(C)C=CC=CC=1>CCOCC>[CH:1]1([C:6]2[C:15]([CH:16]([F:27])[C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:25])([F:26])[F:24])=[CH:19][CH:18]=3)=[C:14]([C:28]3[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=3)[C:13]3[C:12]([CH3:42])([OH:35])[CH2:11][C:10]([CH3:37])([CH3:36])[CH2:9][C:8]=3[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 1140TolueneHCID 25517Ammonium ChlorideHCID 15859006HCID 15859006, compoundHCID 178418348HCID 178418348, compound

Product 1

HCID 9806979HCID 9806979, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

514 mg (1 mmol) of the keto compound from Example XI are dissolved in 50 ml of ether p.a. (which had been dried over a molecular sieve), and the mixture is cooled under argon to −78° C. and admixed dropwise with 3.1 ml (5 mmol, 5 eq.) of methyllithium (1.6 molar solution in ether). The solution is subsequently stored at −30° C. (deep freezer) for 20 hours. The solution is then cooled to −78° C. and admixed with 20 ml of ammonium chloride solution and 40 ml of toluene p.a. The cooling bath is removed and the solution is allowed to warm to room temperature. The organic phase is separated off, the aqueous phase is extracted twice with toluene and the combined organic phases are dried over Na2SO4, filtered and concentrated. The residue—dissolved in toluene—is chromatographed over 500 ml of silica gel using cyclohexane with a little added ethyl acetate as eluent.

Workup

  1. custom(which had been dried over a molecular sieve), and the mixture
  2. customis subsequently stored at −30° C.
  3. customfor 20 hours
  4. temperatureThe solution is then cooled to −78° C.
  5. customThe cooling bath is removed
  6. temperatureto warm to room temperature
  7. customThe organic phase is separated off
  8. extractionthe aqueous phase is extracted twice with toluene
  9. dry with materialthe combined organic phases are dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. dissolutionThe residue—dissolved in toluene—
  13. customis chromatographed over 500 ml of silica gel
  14. additiona little added ethyl acetate as eluent

Sources & evidence

ORD record
ord-bef8a944e2a343b2931b0e68885e692e
Source dataset
uspto-grants-2005_05
Patent number
US06897317B2

Reaction notes

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