Acetic Acid → HCID 66649526, Verbindung

HRID 420289Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 420289
[C:1]([O:5][C:6]([N:8]1[C@@H:16]2[C@H:11]([C@H:12]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([NH:24][C:25]([O:27][CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[O:26])=[C:20]([F:35])[CH:19]=3)[CH2:13][S:14][CH2:15]2)[O:10][C:9]1([CH3:37])[CH3:36])=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(O)=[O:40].OO.[O-]S([O-])(=S)=O.[Na+].[Na+]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[C@@H:16]2[C@H:11]([C@H:12]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([NH:24][C:25]([O:27][CH2:28][C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)=[O:26])=[C:20]([F:35])[CH:19]=3)[CH2:13][S@:14](=[O:40])[CH2:15]2)[O:10][C:9]1([CH3:37])[CH3:36])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Komponenten

6

Edukt 4

HCID 176Acetic AcidHCID 784Hydrogen PeroxideHCID 24477Sodium ThiosulfateHCID 68556594HCID 68556594, Verbindung

Produkt 1

HCID 66649526HCID 66649526, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

To a solution of (3aR*,7S*,7aS*)-7-(4-benzyloxycarbonylamino-3-fluoro-benzyl)-2,2-dimethyl-tetrahydro-1-oxa-5-thia-3-aza-indene-3-carboxylic acid tert-butyl ester (54.1 g, 102 mmol) in THF (500 mL) was added AcOH (200 mL) and H2O2 (27.8 g, 50% in H2O, 408 mmol) at 0-5° C. and the reaction mixture was stirred for 16 h at 25° C. The reaction mixture was slowly added to a cold 25% aq. Na2S2O3 solution, stirred for 3 h at 0-5° C. and extracted with EtOAc. Combined organic layers were washed with water, saturated K2CO3 solution and brine, dried over MgSO4, filtered and evaporated. The crude product was filtered through a short plug of ammonia deactivated silicagel and the title compound was obtained as a 3:2 mixture of the (3aR*,5R*,7S*,7aS*)- and (3aR*,5S*,7S*,7aS*)-diastereoisomer after crystallization from Et2O-hexane: TLC (EtOAc-MeOH 19:1) Rf=0.51; HPLC RtA=2.34 min and 2.38 min; ESIMS [M+H]+=547. Separation of the racemic 3:2 mixture on Chiralpak IC (heptene-EtOH 85:15) and on Chiralpak AD-I (hexane-EtOH-CHCl3 80:10:10) provided the diastereoisomers (3aR,5R,7S,7aS)-7-(4-benzyloxycarbonylamino-3-fluoro-benzyl)-2,2-dimethyl-5-oxo-hexa-hydro-1-oxa-5lambda*4*-thia-3-aza-indene-3-carboxylic acid tert-butyl ester (peak 1 on Chiralpak IC) in >98% ee: [α]D−21.5° (c 1, CHCl3); 1H NMR (600 MHz, DMSO-d6): δ 9.43 (s, 1H), 7.56 (s, 1H), 7.40 (m, 4H), 7.33 (t, 1H), 7.08 (d, 1H), 6.99 (d, 1H), 5.14 (s, 2H), 3.6-3.8 (m, 2H), 3.40 (t, 1H), 2.92 (m, 2H), 2.6-2.8 (m, 3H), 2.37 (t, 1H), 1.55 (s, 3H), 1.50 (s, 3H), 1.41 (s, 9H) and (3aR,5S,7S,7aS)-7-(4-benzyloxycarbonylamino-3-fluoro-benzyl)-2,2-di-methyl-5-oxo-hexahydro-1-oxa-5lambda*4*-thia-3-aza-indene-3-carboxylic acid tert-butyl ester (peak 2 on Chiralpak IC): 1H NMR (600 MHz, DMSO-d6): δ 9.44 (s, 1H), 7.57 (s, 1H), 7.40 (m, 4H), 7.35 (t, 1H), 7.08 (d, 1H), 6.99 (d, 1H), 5.14 (s, 2H), 3.9-4.2 (m, 1H), 3.65 (t, 1H), 2.5-3.5 (m, 6H), 2.25 (m, 1H), 1.51 (s, 6H), 1.42 (s, 9H) followed by the (3aS,5R,7R,7aR)- and (3aS,5S,7R,7aR)-diastereoisomers (peak 3 and peak 4).

Aufarbeitung

  1. stirringstirred for 3 h at 0-5° C.
  2. extractionextracted with EtOAc
  3. washCombined organic layers were washed with water, saturated K2CO3 solution and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. filtrationThe crude product was filtered through a short plug of ammonia deactivated silicagel

Quellen und Nachweise

ORD-Eintrag
ord-d4ba2029460c4fd683d60871cbac9443
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08093406B2

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