Acetone → 1-(Tert-butoxycarbonyl)-4-[2,6-difluoro-4-(benzyloxycarbonyl)aminophenyl]piperazine

HRID 77429

Reaktionsgleichung

Reaktionsgleichung von HRID 77429
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([F:20])=[CH:18][C:17]([NH2:21])=[CH:16][C:15]=2[F:22])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)=O.C(=O)(O)[O-].[Na+].Cl[C:33]([O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:34]>O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[C:15]([F:22])=[CH:16][C:17]([NH:21][C:33]([O:35][CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)=[O:34])=[CH:18][C:19]=2[F:20])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Komponenten

6

Edukt 4

HCID 180AcetoneHCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 45925741tert-Butyl 4-(4-amino-2,6-difluorophenyl)piperazine-1-carboxylate2×

Produkt 1

HCID 214626171-(Tert-butoxycarbonyl)-4-[2,6-difluoro-4-(benzyloxycarbonyl)aminophenyl]piperazineAusbeute 90 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 4-(4-amino-2,6-difluoro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (Intermediate III) (25 g, 0.08 mol), in 1:1 acetone:water (300 mL) was added sodium bicarbonate (15.1 g, 0.18 mol). The resulting solution was cooled to 0° C. and benzyl chloroformate (40 mL, 0.24 mol, 50% solution in toluene) was added dropwise. The reaction mixture was stirred at r.t. and progress of the reaction was monitored by TLC. On completion, solvent was evaporated under reduced pressure and the residue was dissolved in ethyl acetate (500 mL). The organic layer was washed with water (2×50 mL), brine (100 mL), dried over anhydrous sodium sulphate and concentrated in vacuo. The residue was purified by column chromatography (silica gel, 2:3 ethyl acetate:Pet. ether) to provide title compound (32 g, 90%) as off white solid.

Aufarbeitung

  1. customOn completion, solvent was evaporated under reduced pressure
  2. dissolutionthe residue was dissolved in ethyl acetate (500 mL)
  3. washThe organic layer was washed with water (2×50 mL), brine (100 mL)
  4. dry with materialdried over anhydrous sodium sulphate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (silica gel, 2:3 ethyl acetate:Pet. ether)

Quellen und Nachweise

ORD-Eintrag
ord-30f02fab636b452cb88bf9d04bc20bcf
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841306B2

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