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 1051352ノート

反応式

HRID 1051352 の反応式
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]

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 78391,2-Dibromoethane触媒HCID 8028Tetrahydrofuran溶媒

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-d0a2c3e6d6c84dc3b4774f87a9361118
出典データセット
uspto-grants-2016_07
特許番号
US09388171B2

反応ノート

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