(4R)-4-phenyl-1,3-oxazolidin-2-one → 3-[(2-fluorophenyl)-acetyl]-4(R)-phenyl-2-oxazolidinone

HRID 1638163

Reaktionsgleichung

Reaktionsgleichung von HRID 1638163
[C:1]1([C@@H:7]2[CH2:11][O:10][C:9](=[O:12])[NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH2:20][C:21](Cl)=[O:22].[Na+].C([O-])(=O)CC(CC(O)=O)(C(O)=O)O>C1(C)C=CC=CC=1>[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH2:20][C:21]([N:8]1[C@H:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:11][O:10][C:9]1=[O:12])=[O:22]

Komponenten

5

Edukt 3

HCID 730425(4R)-4-phenyl-1,3-oxazolidin-2-oneHCID 140040112-(2-Fluorophenyl)acetyl chlorideHCID 23666341Monosodium Citrate

Produkt 1

HCID 111506973-[(2-fluorophenyl)-acetyl]-4(R)-phenyl-2-oxazolidinone

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

A solution of 46.0 g of (R)-4-phenyl-2-oxazolidinone in 300 g (338 mL) of peroxide-free tetrahydrofuran is cooled to -5 to 0° C. (bath temperature -10 to -5° C.) over a period of 15 minutes. 145.2 g (166.8 mL) of 25% w/w potassium t-amylate/toluene solution is added over a period of 25 minutes while maintaining an internal temperature below 0° C. The reaction mixture is warmed to 20±5° C. within 1 hour and stirred at this temperature for 2.5-3 hours. The mixture is cooled to -15 to -5° C. over a period of 30 minutes, and crude 2-fluorobenzenacetyl chloride (obtained above) is added over a period of 45 minutes while maintaining an internal temperature below -5° C. (bath temperature -15 to -10° C.). After the addition is completed, the mixture is warmed to 20±5° C. over a period of 1 hour, and diluted with 100 mL of toluene. This is added to 500 mL of saturated citric acid monosodium salt solution (100 g in 450 g of water) and the mixture is stirred for 5 minutes. The organic layer is separated, and washed with 1 L of sodium chloride solution (200 g in 800 g of water) in two equal portions of 500 mL each. The solution is concentrated to dryness under reduced pressure (66-76 mm Hg, bath temperature 65-70° C.) to obtain 3-[2-(2-fluorophenyl)-1-oxoethyl]-4(R)-phenyl-2-oxazolidinone as a semi-solid. The semi-solid is suspended in 450 mL of t-butyl methyl ether and the mixture is heated to reflux (53-58° C.) to obtain a solution; 225 mL of t-butyl methyl ether is then distilled off at atmospheric pressure (bath temperature 60-65° C.). The resulting mixture is cooled to 20-25° C., and stirred at this temperature for 16 hours, then cooled to -5 to 0° C. and stirred at this temperature for additional 2 hours and filtered. The resulting solid is dried under vacuum (66-76 mm Hg) at 45-50° C. for 12 hours to obtain 3-[2-(2-fluorophenyl)-1-oxoethyl]-4(R)-phenyl-2-oxazolidinone as a white crystalline solid. Alternately, 3-[2-(2-fluorophenyl)-1-oxoethyl]-4-(R)-phenyl-2-oxazolidinone is prepared as follows:

Aufarbeitung

  1. temperaturewhile maintaining an internal temperature below 0° C
  2. temperatureThe mixture is cooled to -15 to -5° C. over a period of 30 minutes
  3. temperaturewhile maintaining an internal temperature below -5° C. (bath temperature -15 to -10° C.)
  4. additionAfter the addition
  5. temperaturethe mixture is warmed to 20±5° C. over a period of 1 hour
  6. stirringthe mixture is stirred for 5 minutes
  7. customThe organic layer is separated
  8. washwashed with 1 L of sodium chloride solution (200 g in 800 g of water) in two equal portions of 500 mL each
  9. concentrationThe solution is concentrated to dryness under reduced pressure (66-76 mm Hg, bath temperature 65-70° C.)

Quellen und Nachweise

ORD-Eintrag
ord-fd0f27efccf44ff7a02123293d5bac67
Quelldatensatz
uspto-grants-2000_03
Patentnummer
US06043365

Verknüpfte Notizen

Wird geladen…