Methanol → HCID 178448629, Verbindung

HRID 1931101Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1931101
[CH3:1][C:2]([CH3:5])([O-:4])[CH3:3].[K+].[CH2:7]([N:11]1[N:12]([CH3:34])[C:13]([C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:14]/[C:15]/1=[N:16]\[C:17](=[O:29])[C:18]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:19]=1F)[CH2:8][CH2:9][CH3:10].CC[O:37]C(C)=O.CO>C1COCC1.CCN(CC)CC>[CH2:7]([N:11]1[N:12]([CH3:34])[C:13]([C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:14]/[C:15]/1=[N:16]\[C:17](=[O:29])[C:18]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:19]=1[O:37][CH2:1][C:2]([OH:4])([CH3:5])[CH3:3])[CH2:8][CH2:9][CH3:10]

Komponenten

7

Edukt 4

HCID 887MethanolHCID 8857Ethyl Acetate2×HCID 23665647Potassium tert-butoxideHCID 178448620HCID 178448620, Verbindung

Produkt 1

HCID 178448629HCID 178448629, VerbindungAusbeute 57 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

To a solution of Example 81D (7.6 g, 84 mmol) in THF (300 mL) at 0° C. was added potassium tert-butoxide (18.9 g, 168 mmol). The ice bath was removed and the mixture was stirred for 45 min then a solution of Example 81C (22.4 g, 56.1 mmol) in THF (100 mL) was added. The mixture was stirred for 2 hours at ambient temperature then partitioned between saturated aqueous NaHCO3 (100 mL) and EtOAc (100 mL). The layers were separated and the aqueous phase was extracted with EtOAc (3×20 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. Purification by column chromatography (SiO2, 50% hexanes/EtOAc then 100% EtOAc then 9:1:0.1 EtOAc:MeOH:Et3N) afforded the title compound (15 g, 31.9 mmol, 57% yield). 1H NMR (300 MHz, CDCl3) δ ppm 0.95 (t, J=7.3 Hz, 3H) 1.28 (s, 6H) 1.32-1.42 (m, 2H) 1.42 (s, 9H) 1.61-1.72 (m, 2H) 3.75 (s, 3H) 4.03 (s, 2H) 4.27 (dd, J=7.8 Hz, 2H) 6.16 (s, 1H) 7.00 (d, J=8.5 Hz, 1H) 6.99 (s, 1H) 7.51 (dd, J=8.6, 1.9 Hz, 1H) 8.13 (d, J=2.4 Hz, 1 H); MS (DCI/NH3) m/z 470 (M+H)+; Anal. calculated for C24H34F3N3O3: Calc: C, 61.39; H, 7.30; N, 8.95. Found: C, 61.33; H, 7.38; N, 8.91.

Aufarbeitung

  1. customThe ice bath was removed
  2. stirringThe mixture was stirred for 2 hours at ambient temperature
  3. customthen partitioned between saturated aqueous NaHCO3 (100 mL) and EtOAc (100 mL)
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with EtOAc (3×20 mL)
  6. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification by column chromatography (SiO2, 50% hexanes/EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-6b67f329bdb942ffb0863c182a12b765
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08188135B2

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