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 1051352노트

반응식

HRID 1051352 반응식
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]

참가 물질

6

반응물 3

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

생성물 1

HCID 86711993(R)-N-((S)-(4-chloro-3-fluorophenyl)(1-methyl-1H-pyrazol-4-yl)methyl)-2-methylpropane-2-sulfinamide수율 45.1%

시약·촉매·용매 2

HCID 78391,2-Dibromoethane촉매HCID 8028Tetrahydrofuran용매

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-d0a2c3e6d6c84dc3b4774f87a9361118
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09388171B2

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