Hydrochloric Acid → N-[(2R*,3S*)-5-fluoro-3-hydroxy-2-methylpentanoyl]-2-benzoxazolone

HRID 736025

Reaktionsgleichung

Reaktionsgleichung von HRID 736025
[C:1]([N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[O:7][C:6]1=[O:14])(=[O:4])[CH2:2][CH3:3].CN1CCOCC1.[F:22][CH2:23][CH2:24][CH:25]=[O:26].Cl>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl>[F:22][CH2:23][CH2:24][C@H:25]([OH:26])[C@@H:2]([CH3:3])[C:1]([N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[O:7][C:6]1=[O:14])=[O:4]

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 8437913-Propionyl-2-benzoxazolinoneHCID 201949333-Fluoropropanal

Produkt 1

HCID 51064156N-[(2R*,3S*)-5-fluoro-3-hydroxy-2-methylpentanoyl]-2-benzoxazoloneAusbeute 74,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24193Titanium TetrachlorideKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Titanium tetrachloride (15.8 mL, 144 mmol) was added over 5 minutes to a vigorously stirred solution of N-propionyl-2-benzoxazolone (25.0 g, 131 mmol) in anhydrous CH2Cl2 (250 mL) cooled on ice and maintained under inert atmosphere. After 10 minutes, the yellow slurry was treated with N-methylmorpholine (15.8 mL, 144 mmol) over 5 minutes, and stirring was continued for an additional 45 minutes. A 0.48 M solution of 3-fluoropropanal (310 mL, 150 mmol) was added to the dark red solution over 30 minutes, such that the internal temperature remained below 10° C. After addition was complete, the mixture was stirred for an additional 30 minutes on ice, then at warm to ambient temperature an additional 1 hour. The reaction was treated with 250 mL of 2 N HCl with vigorous mixing, and the phases were separated, discarding the aqueous phase. The organic phase was filtered through a pad of silica gel (10 g), which was subsequently washed with 100 mL of methyl tert-butyl ether (MTBE). The combined eluates were evaporated to dryness. The resulting solid mass was triturated with MTBE, allowed to stand for 1 hour, then collected by vacuum filtration, yielding 26 gm of crystalline product. 1H-NMR: δ 8.07-8.02 (m, 1H), 7.29-7.18 (m, 3H), 4.77-4.05 (m, 2H), 4.31 (m, 1H), 3.96 (dq, J=7, 3 Hz, 1H), 2.00-1.79 (m, 2H), 1.34 (d, J=7 Hz, 3H). 13C-NMR: δ 176.1, 151.1, 142.2, 127.7, 125.6, 125.0, 116.2, 110.0, 82.0, 80.4, 68.0, 43.8, 34.7, 34.5, 10.4.

Aufarbeitung

  1. temperaturecooled on ice
  2. temperaturemaintained under inert atmosphere
  3. waitwas continued for an additional 45 minutes
  4. customremained below 10° C
  5. additionAfter addition
  6. stirringthe mixture was stirred for an additional 30 minutes on ice
  7. customthe phases were separated
  8. filtrationThe organic phase was filtered through a pad of silica gel (10 g), which
  9. washwas subsequently washed with 100 mL of methyl tert-butyl ether (MTBE)
  10. customThe combined eluates were evaporated to dryness
  11. customThe resulting solid mass was triturated with MTBE
  12. waitto stand for 1 hour
  13. filtrationcollected by vacuum filtration

Quellen und Nachweise

ORD-Eintrag
ord-62bb23469a654b519b17fcf46fe759f3
Quelldatensatz
uspto-grants-2009_09
Patentnummer
US07595300B2

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