Hydrochloric Acid → HCID 86706858, Verbindung

HRID 717877

Reaktionsgleichung

Reaktionsgleichung von HRID 717877
C([Li])CCC.[F:6][C:7]([F:29])([F:28])[C:8]1[N:13]=[C:12]([O:14][CH:15]2[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][CH2:16]2)[CH:11]=[CH:10][CH:9]=1.[O:30]1[CH2:34][CH2:33]OS1(=O)=O.Cl.O.C(=O)(O)[O-].[Na+]>O1CCCC1.[Cl-].[Na+].O>[NH:18]1[CH2:17][CH2:16][CH:15]([O:14][C:12]2[CH:11]=[C:10]([CH2:33][CH2:34][OH:30])[CH:9]=[C:8]([C:7]([F:6])([F:28])[F:29])[N:13]=2)[CH2:20][CH2:19]1

Komponenten

9

Edukt 6

HCID 313Hydrochloric AcidHCID 962WaterHCID 140751,3,2-Dioxathiolane, 2,2-dioxideHCID 516892Sodium BicarbonateHCID 86706857Tert-butyl 4-{[6-(trifluoromethyl)pyridin-2-yl]oxy}piperidine-1-carboxylateHCID 178418339Butyllithium

Produkt 1

HCID 86706858HCID 86706858, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 57417360Sodium chloride; waterLösungsmittel

Versuchsvorschrift

2.5 M n-Butyllithium in hexanes (1.2 mL, 2.9 mmol) was added dropwise to a solution of tert-butyl 4-{[6-(trifluoromethyl)pyridin-2-yl]oxy}piperidine-1-carboxylate (0.50 g, 1.4 mmol, from Step 1) in tetrahydrofuran (8.0 mL) at −78° C. The reaction was stirred at this temperature for 1.5 hours, and 1,3,2-dioxathiolane 2,2-dioxide (0.36 g, 2.9 mmol, Aldrich) in Tetrahydrofuran (2.0 mL) was added. The mixture was allowed to warm to room temperature and stir overnight. 12 N Hydrogen chloride in water (0.72 mL, 8.7 mmol) was added to the mixture. The mixture was stirred at room temperature for 4 hours. The mixture was then treated with saturated sodium bicarbonate to pH between 7 and 8, and brine was added. The mixture was then extracted with DCM four times. The combined extracts were dried over sodium sulfate, filtered and concentrated. Preparative HPLC-MS (C18 eluting with a gradient of MeCN/H2O containing 0.15% NH4OH) was used to purify the product. It was the second peak to elute having the desired mass. 1H NMR (300 MHz, CD3OD) δ 7.24 (s, 1H), 6.86 (s, 1H), 5.16 (tt, J=8.4, 3.9 Hz, 1H), 3.80 (t, J=6.3 Hz, 2H), 3.06 (dt, J=12.6, 4.6 Hz, 2H), 2.85 (t, J=6.3 Hz, 2H), 2.73 (ddd, J=12.7, 9.5, 3.2 Hz, 2H), 2.13-1.93 (m, 2H), 1.68 (dtd, J=13.0, 9.1, 3.9 Hz, 2H). 19F NMR (282 MHz, CD3OD) δ −70.29 (s). LCMS (M+H)+: 291.1

Aufarbeitung

  1. stirringstir overnight
  2. stirringThe mixture was stirred at room temperature for 4 hours
  3. additionwas added
  4. extractionThe mixture was then extracted with DCM four times
  5. dry with materialThe combined extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. washPreparative HPLC-MS (C18 eluting with a gradient of MeCN/H2O containing 0.15% NH4OH)
  9. customto purify the product
  10. washto elute

Quellen und Nachweise

ORD-Eintrag
ord-ccfcd1d1b8694d098c3ea0452072bf5a
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09193733B2

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