Allyl bromide → (3S)-1-allyl-3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexanol

HRID 527042Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 527042
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][CH2:12][C:11](=[O:15])[CH2:10]2)[C:5]([F:16])=[CH:4][N:3]=1.Br[CH2:18][CH:19]=[CH2:20].[NH4+].[Cl-]>CN(C=O)C.[Zn]>[CH2:20]([C:11]1([OH:15])[CH2:12][CH2:13][CH2:14][C@H:9]([NH:8][C:6]2[C:5]([F:16])=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=2)[CH2:10]1)[CH:19]=[CH2:18]

Komponenten

6

Edukt 3

HCID 7841Allyl bromideHCID 25517Ammonium ChlorideHCID 86667417(S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexanone2×

Produkt 1

HCID 86667442(3S)-1-allyl-3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexanol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 23994ZincKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of (3S)-3-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]cyclohexanone, 29b, (0.60 g, 2.46 mmol) and 3-bromoprop-1-ene (0.43 mL, 4.92 mmol) in DMF was added Zn dust (0.32 g, 4.92 mmol). The reaction was stirred at room temperature for 3 days. The mixture was diluted into aqueous saturated NH4Cl solution, extracted twice with EtOAc. The combined organic phases were washed twice with brine, dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography using 0-50% EtOAc/hexanes gradient to afford 553 mg of desired product, 58a, as an oil. LC/MS two peaks corresponding to two diastereomeric products: 286.4 (M+H), RT=3.41 and 3.78.

Aufarbeitung

  1. extractionextracted twice with EtOAc
  2. washThe combined organic phases were washed twice with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-94c50de7fba841c08022a52fe446d31f
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09345708B2

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