Acetic Acid → Maribavir Impurity 57

HRID 724857

Reaktionsgleichung

Reaktionsgleichung von HRID 724857
[Br:1][C:2]1[N:6]([C@@H:7]2[O:19][C@H:18]([CH2:20][O:21][C:22](=[O:24])[CH3:23])[C@@H:13]([O:14]C(=O)C)[C@H:8]2[O:9]C(=O)C)[C:5]2[CH:25]=[C:26]([Cl:30])[C:27]([Cl:29])=[CH:28][C:4]=2[N:3]=1.CC([O-])=O.[K+].CC(O)=O>CO.O>[C:22]([O:21][CH2:20][C@H:18]1[O:19][C@@H:7]([N:6]2[C:5]3[CH:25]=[C:26]([Cl:30])[C:27]([Cl:29])=[CH:28][C:4]=3[N:3]=[C:2]2[Br:1])[C@H:8]([OH:9])[C@@H:13]1[OH:14])(=[O:24])[CH3:23]

Komponenten

5

Edukt 3

HCID 176Acetic AcidHCID 466020[(2R,3R,4R,5R)-3,4-diacetoxy-5-(2-bromo-5,6-dichloro-benzimidazol-1-yl)tetrahydrofuran-2-yl]methyl acetateHCID 517044Potassium Acetate

Produkt 1

HCID 22876558Maribavir Impurity 57

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 22242641Methanol--water (1/1)Lösungsmittel

Versuchsvorschrift

A mixture of 52a (1.048 g, 2.0 mmol) and KOAc (0.98 g, 10.0 mmol) in MeOH/H2O (40 mL/4 mL) was stirred at room temperature for 24 hr. AcOH (0.572 mL, 10.0 mmol) was added and stirring was continued at room temperature for 15 min. The reaction mixture was evaporated and the residue was partitioned between. EtOAc/H2O (75 mL/75 mL). The EtOAc layer was washed with sat. NaCl solution (75 mL), dried (Na2 SO4), and evaporated. The residue was chromatographed on a silica column (1.9×24 cm, eluted with CHCl3, 2%, 3%, 4% MeOH/CHCl3). Evaporation of fractions 15-27 (15 mL per fraction) and recrystallization from MeOH gave 0.50 g (2 crops, 57%) of 52b as white crystals. MP: 85°-95° C. (melted slowly over a large range) MS: (El) m/e 437.9398 (15%, M+ =437.9385). 1H NMR (DMSO-d6): d 8.00, 7.95 (2×s, 2, 7-H and 4-H), 5.90 (d, 1, 1'-H, J1'-2' =7.5 Hz), 5.58 (d, 1,2'-OH, J2'-2'OH=6.5 Hz), 5.46 (d, 1, 3'-OH, J3'-3'OH =4.5 Hz), 4.44 (dd, 1, 5'-H, J5'-4' =4.5 Hz, J5'-5' =12.5 Hz), 4.43 (m, 1,2'-H, J2'-3' =6.0 Hz), 4.24 (dd, 1,5"-H, J5"-4' =2.0 Hz), 4.16 (m, 1, 4'-H, J3'-4' =3.0 Hz), 4.11 (m, 1, 3'-H), 2.15 (s, 3, 5'-OAc). 13C NMR (DMSO-d6): d 169.96 (COCH3), 142.57 (C3a), 132.49, 132.42 (C2 and C7a), 125.78, 125.74 (C5 and C6), 120.14 (C4), 113.28 (C7), 90.32 (C1'), 82.56 (C4'), 71.27 (C2'), 68.99 (C3'), 63.34 (C5'), 20.58 (COCH3). Anal. Calcd. for C14H13BrCl2N2O5 : C, 38.21; H, 2.98; N, 6.37. Found: C, 38.37; H, 2.86; N, 6.27.

Aufarbeitung

  1. stirringstirring
  2. waitwas continued at room temperature for 15 min
  3. customThe reaction mixture was evaporated
  4. customthe residue was partitioned between
  5. washThe EtOAc layer was washed with sat. NaCl solution (75 mL)
  6. customdried (Na2 SO4)
  7. customevaporated
  8. customThe residue was chromatographed on a silica column (1.9×24 cm, eluted with CHCl3, 2%, 3%, 4% MeOH/CHCl3)
  9. customEvaporation of fractions 15-27 (15 mL per fraction) and recrystallization from MeOH

Quellen und Nachweise

ORD-Eintrag
ord-0fb3be6a845943fdb86797ad21b18b0b
Quelldatensatz
uspto-grants-1998_01
Patentnummer
US05705490

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