Hydrochloric Acid → beta-(R)-(2-fluorophenyl)-gamma,2-dioxo-4(R)-phenyl-3-oxazolidinebutyronitrile

HRID 566270

Reaktionsgleichung

Reaktionsgleichung von HRID 566270
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([N:11]1[C@H:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:14][O:13][C:12]1=[O:22])=[O:10].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].Br[CH2:34][C:35]#[N:36].[Na+].[Cl-].Cl>O1CCCC1.O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:8]([C:9](=[O:10])[N:11]1[C@H:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:14][O:13][C:12]1=[O:22])[CH2:34][C:35]#[N:36]

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 11534BromoacetonitrileHCID 2733832Lithium HexamethyldisilazideHCID 111506973-[(2-fluorophenyl)-acetyl]-4(R)-phenyl-2-oxazolidinone

Produkt 1

HCID 11089040beta-(R)-(2-fluorophenyl)-gamma,2-dioxo-4(R)-phenyl-3-oxazolidinebutyronitrile

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-2.5 °C

Versuchsvorschrift

A solution of 546 g of 3-[2-(2-fluorophenyl)-1-oxoethyl]-4(R)-phenyl-2-oxazolidinone in 2,180 mL of peroxide-free tetrahydrofuran is cooled to an internal temperature of −5 to −8° C. A solution of 1,773 mL of lithium hexamethyldisilazide in tetrahydrofuran (1M) is added over a period of 55 minutes, while maintaining an internal temperature of 0 to −5° C. The solution is stirred at an internal temperature of 0 to −5° C. for 1 hour and then cooled to an internal temperature of −20° C. 150 mL of Bromoacetonitrile is added over a period of 40 minutes, while maintaining an internal temperature of −15 to −20° C. The reaction mixture is stirred at an internal temperature of −15 to −20° C. for 4.5 hours and added to a solution of 478 g of NaCl in 2,164 mL of water and 214 g of concentrated HCl cooled to an internal temperature of 0 to 5° C., over a period of 20 minutes, while maintaining the internal temperature below 9° C. After addition of 500 mL of tetrahydrofuran, the slurry is stirred for 15 minutes at an internal temperature of 5 to 8° C., and then warmed to room temperature (17 to 19° C.) over a period of 30 minutes. The organic layer is separated and washed with a solution of 632 g of NaCl in 2,180 mL of water. The slurry is stirred for 15 minutes, the organic layer is separated and concentrated under reduced pressure (20 mm Hg; bath temperature 45° C.) to a final volume of 1.4-1.6 L. 2,500 mL of t-Butyl methyl ether is added and the slurry is vigorously stirred for 1 hour at room temperature (18 to 20° C.). The solid is collected and washed with 2×150 mL of t-butyl methyl ether and dried at 45 to 50° C. (20 mm Hg) for 20 hours to obtain β-(R)-(2-fluorophenyl)-γ,2-dioxo-4(R)-phenyl-3-oxazolidinebutyronitrile as an off-white crystalline solid.

Aufarbeitung

  1. temperaturecooled to an internal temperature of −20° C
  2. temperaturewhile maintaining an internal temperature of −15 to −20° C
  3. stirringThe reaction mixture is stirred at an internal temperature of −15 to −20° C. for 4.5 hours
  4. temperaturecooled to an internal temperature of 0 to 5° C., over a period of 20 minutes
  5. temperaturewhile maintaining the internal temperature below 9° C
  6. stirringthe slurry is stirred for 15 minutes at an internal temperature of 5 to 8° C.
  7. temperaturewarmed to room temperature (17 to 19° C.) over a period of 30 minutes
  8. customThe organic layer is separated
  9. washwashed with a solution of 632 g of NaCl in 2,180 mL of water
  10. stirringThe slurry is stirred for 15 minutes
  11. customthe organic layer is separated
  12. concentrationconcentrated under reduced pressure (20 mm Hg; bath temperature 45° C.) to a final volume of 1.4-1.6 L
  13. addition2,500 mL of t-Butyl methyl ether is added
  14. stirringthe slurry is vigorously stirred for 1 hour at room temperature (18 to 20° C.)
  15. customThe solid is collected
  16. washwashed with 2×150 mL of t-butyl methyl ether
  17. customdried at 45 to 50° C. (20 mm Hg) for 20 hours

Quellen und Nachweise

ORD-Eintrag
ord-21d9504785e343e194463f720890c1fe
Quelldatensatz
uspto-grants-2001_01
Patentnummer
US06174888B1

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