Diethyl Ether → HCID 24765404, Verbindung

HRID 1255121

Reaktionsgleichung

Reaktionsgleichung von HRID 1255121
Cl.[CH3:2]NOC.C(N(CC)CC)C.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=1[CH2:23][C:24](Cl)=O.C[Mg]Br.CCOCC.BrC1C=C(C2[S:46][C:45]([NH:47][C:48](=[O:57])[C:49]3[C:54]([F:55])=[CH:53][CH:52]=[CH:51][C:50]=3[F:56])=[N:44]C=2C)C=CN=1>C(Cl)Cl>[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=1[C:23]1[S:46][C:45]([NH:47][C:48](=[O:57])[C:49]2[C:54]([F:55])=[CH:53][CH:52]=[CH:51][C:50]=2[F:56])=[N:44][C:24]=1[CH3:2]

Komponenten

8

Edukt 6

HCID 3283Diethyl EtherHCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 596088(2,5-Dimethoxyphenyl)acetyl chlorideHCID 24765026HCID 24765026, VerbindungHCID 178418573HCID 178418573, Verbindung

Produkt 1

HCID 24765404HCID 24765404, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

Into a slurry of N,O-dimethylhydroxylamine hydrochloride (732 mg, 7.5 mmol) in CH2Cl2 (10.0 mL) at room temperature was added triethylamine (1.52 g, 15.0 mmol). The mixture was stirred at room temperature for 10 minutes, cooled to −78° C. Into the reaction mixture a solution of 2-(2,5-dimethoxyphenyl)acetyl chloride (1.08 g, 5.0 mmol) in CH2Cl2 (5.0 mL) was added dropwise. The mixture was gradually warm to room temperature. After 30 minutes at room temperature, the reaction mixture was quenched by slow addition of a solution of saturated NaHCO3, extracted with CH2Cl2. The extract was dried (Na2SO4), filtered and concentrated to the crude 32a (950 mg). The crude amide was taken up in THF (10.0 mL). Into the resulting solution at 0° C. was added dropwise a solution of 3M methylmagnesium bromide in ether (2.00 mL, 6.00 mmol). The mixture was stirred at room temperature for 3 hours, cooled to 0° C., quenched with ice. The mixture was acidified with 6N HCl. After 1 hour at room temperature, the mixture was neutralized with a solution of saturated NaHCO3, extracted with CH2Cl2. The extract was dried (Na2SO4), filtered and concentrated. The resulting methyl ketone was used directly without purification to prepare Compound 55 in the similar manner as described for the preparation of Compound 27.

Aufarbeitung

  1. temperaturecooled to −78° C
  2. temperatureThe mixture was gradually warm to room temperature
  3. waitAfter 30 minutes at room temperature
  4. customthe reaction mixture was quenched by slow addition of a solution of saturated NaHCO3
  5. extractionextracted with CH2Cl2
  6. dry with materialThe extract was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated to the crude 32a (950 mg)
  9. stirringThe mixture was stirred at room temperature for 3 hours
  10. temperaturecooled to 0° C.
  11. customquenched with ice
  12. waitAfter 1 hour at room temperature
  13. extractionextracted with CH2Cl2
  14. dry with materialThe extract was dried (Na2SO4)
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customThe resulting methyl ketone was used directly without purification
  18. customto prepare Compound 55 in the similar manner

Quellen und Nachweise

ORD-Eintrag
ord-2554f3d6e50e40f0856d6940d50b7843
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08455658B2

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