4-Bromo-1-chloro-2-fluorobenzene → (R)-N-((S)-(4-chloro-3-fluorophenyl)(1-methyl-1H-pyrazol-4-yl)methyl)-2-methylpropane-2-sulfinamide

HRID 1051352Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1051352
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([F:9])[CH:3]=1.[Mg].[CH3:11][C:12]([S@:15](/[N:17]=[CH:18]/[C:19]1[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=1)=[O:16])([CH3:14])[CH3:13]>C1COCC1.BrCCBr>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([C@@H:18]([C:19]2[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=2)[NH:17][S@@:15]([C:12]([CH3:14])([CH3:13])[CH3:11])=[O:16])=[CH:3][C:4]=1[F:9]

Komponenten

6

Edukt 3

HCID 27246904-Bromo-1-chloro-2-fluorobenzeneHCID 5462224MagnesiumHCID 89998978(NE,R)-2-methyl-N-[(1-methylpyrazol-4-yl)methylidene]propane-2-sulfinamide

Produkt 1

HCID 86711993(R)-N-((S)-(4-chloro-3-fluorophenyl)(1-methyl-1H-pyrazol-4-yl)methyl)-2-methylpropane-2-sulfinamideAusbeute 45,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 78391,2-DibromoethaneKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a mixture of 4-bromo-1-chloro-2-fluorobenzene (11.7 g, 56.0 mmol) and magnesium turnings (2.1 g, 84 mmol) in THF (150 mL) at RT was added a few drops of 1,2-dibromoethane (1.1 g, 5.6 mmol). The mixture was stirred at RT for 1.5 h. After cooling to −78° C., (R,E)-2-methyl-N-((1-methyl-1H-pyrazol-4-yl)methylene)propane-2-sulfinamide (4.00 g, 18.7 mmol) was added and stirred at −78° C. for 6 h. The reaction was quenched with aq. NH4Cl solution and extracted with EtOAc. The combined organic layers were dried (MgSO4), filtered, and concentrated. The crude product was purified by SiO2 chromatography eluting with DCM/MeOH (150:1) to afford the 2.9 g (45%) of (R)—N—((S)-(4-chloro-3-fluorophenyl)(1-methyl-1H-pyrazol-4-yl)methyl)-2-methylpropane-2-sulfinamide (48). LCMS (ESI) m/z: 344.1 [M+H]+.

Aufarbeitung

  1. temperatureAfter cooling to −78° C.
  2. stirringstirred at −78° C. for 6 h
  3. customThe reaction was quenched with aq. NH4Cl solution
  4. extractionextracted with EtOAc
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by SiO2 chromatography
  9. washeluting with DCM/MeOH (150:1)

Quellen und Nachweise

ORD-Eintrag
ord-d0a2c3e6d6c84dc3b4774f87a9361118
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09388171B2

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