Hydrochloric Acid → Ether hydrochloride

HRID 1096699Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1096699
[C:1]1([CH3:14])[CH:6]=[CH:5][C:4]([C:7]23[CH2:12][CH:11]2[CH2:10][C:9](=[O:13])[CH2:8]3)=[CH:3][CH:2]=1.[C:15]([O-])(=O)[CH3:16].[NH4+].[BH3-]C#[N:22].[Na+].[ClH:24].C#N>CO>[ClH:24].[C:1]1([CH3:14])[CH:6]=[CH:5][C:4]([C:7]23[CH2:12][CH:11]2[CH2:10][CH:9]([NH2:22])[CH2:8]3)=[CH:3][CH:2]=1.[ClH:24].[CH2:15]([O:13][CH2:9][CH3:10])[CH3:16]

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 768Hydrogen CyanideHCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 597791441-p-Tolyl-bicyclo[3.1.0]hexan-3-one

Produkt 2

HCID 10953452Ether hydrochlorideHCID 667817491-p-Tolyl-bicyclo[3.1.0]hexan-3-amine hydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a solution of 1-p-tolyl-bicyclo[3.1.0]hexan-3-one (140 mg; 0.75 mmol) in methanol (30 mL) was added ammonium acetate (5.7 g; 100 equivalent) and NaCNBH3 (472 mg; 7.5 mmol). The mixture was heated to 60° C. and stirred for 2 hours. The reaction mixture was cooled to 10° C., and acidified with 1 N HCl (6 mL) taking care that the flask was vented into a bleach solution due to HCN evolution. The reaction mixture was concentrated at 30° C., and the resulting aqueous layer was diluted with H2O (10 mL). The aqueous layer was then extracted with ethyl acetate (15 mL) to remove nonpolar impurities. The aqueous layer was then adjusted to pH 9 with 1N NaOH, and the aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated to an oily residue. The oil was then dissolved in diethyl ether (5 mL), and the HCl salt was formed by slowly adding HCl/diethyl ether solution (0.5 mL). The slurry was stirred for 30 minutes before filtration. The solids were rinsed with diethyl ether (5 mL) and the compound was quickly transferred to a vacuum dessicator and dried under vacuum for 12 hours to afford a white solid (120 mg; 0.54 mmol; 72%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.66-0.69 (m, 1 H) 0.76-0.79 (m, 1H) 1.10-1.20 (m, 1H) 1.52-1.57 (m, 1 H) 1.68-1.73 (dd, 1 H) 1.90-2.05 (m, 1 H) 2.11 (s, 3H) 2.19-2.29 (m, 1 H) 2.36-2.71 (m, 2 H) 3.08-3.29 (m, 1 H) 3.44-3.89 (m, 1 H) 6.71-7.01 (m, 4 H)). 13C NMR (100 MHz, CHLOROFORM-d) δ ppm 17.10 (s, 1 C) 21.16 (s, 1 C) 24.33 (s, 1 C) 24.70 (s, 1 C) 26.84 (s, 1 C) 30.53 (s, 1 C) 33.10 (s, 1C) 33.92 (s, 1 C) 35.52 (s, 1C) 37.80 (s, 1C) 40.27 (s, 1 C) 49.20 (s, 1 C) 53.23 (s, 1 C) 126.50 (s, 1 C) 126.58 (s, 1 C) 129.26 (s, 1 C) 135.74 (s, 1 C) 140.22 (s, 1 C) 140.58 (s, 1 C). MS (M+1) 188, HPLC purity 99% (AUC).

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to 10° C.
  2. concentrationThe reaction mixture was concentrated at 30° C.
  3. additionthe resulting aqueous layer was diluted with H2O (10 mL)
  4. extractionThe aqueous layer was then extracted with ethyl acetate (15 mL)
  5. customto remove nonpolar impurities
  6. extractionthe aqueous layer was extracted with ethyl acetate (2×20 mL)
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to an oily residue
  10. dissolutionThe oil was then dissolved in diethyl ether (5 mL)

Quellen und Nachweise

ORD-Eintrag
ord-6b7c8770aa634248b536b01cea551e6f
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08138377B2

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