Hydrochloric Acid → Ether hydrochloride

HRID 1096715Notes

Reaction equation

HRID 1096715 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]23[CH2:14][CH:13]2[CH2:12][C:11](=O)[CH2:10]3)[CH:5]=[CH:6][C:7]=1[Cl:8].[CH3:16][NH:17][CH3:18].[BH3-][C:20]#N.[Na+].[ClH:23].[CH3:24][OH:25]>>[ClH:1].[CH3:16][N:17]([CH3:18])[CH:11]1[CH2:12][CH:13]2[C:9]([C:4]3[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=3)([CH2:14]2)[CH2:10]1.[ClH:23].[CH2:24]([O:25][CH2:2][CH3:7])[CH3:20]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 674DimethylamineHCID 887MethanolHCID 5003444Sodium cyanoborohydrideHCID 597791481-(3,4-Dichlorophenyl)bicyclo[3.1.0]hexan-3-one

Product 2

HCID 10953452Ether hydrochlorideHCID 66781217N,N-dimethyl-1-(3,4-dichlorophenyl)bicyclo[3.1.0]hexan-3-amine hydrochloride

Procedure

To a solution of 1-(3,4-dichlorophenyl)bicyclo[3.1.0]hexan-3-one (112 mg; 0.46 mmol) in methanol (4 mL) was added dimethylamine (2M in THF; 2 mL) and NaCNBH3 (37.5 mg; 0.60 mmol; 1.3 eq). The mixture was stirred at room temperature overnight. The reaction mixture was cooled to 10° C., and acidified with 1 N HCl (4 mL). The reaction mixture was concentrated at 30° C., and the resulting aqueous layer was diluted with H2O (8 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 give the title compound as a beige solid (84 mg; 73%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.68-0.77 (m, 1H) 1.11 (t, 1 H) 1.67-1.79 (m, 1 H) 2.03-2.14 (m, 2 H) 2.36-2.55 (m, 2 H) 2.57-2.72 (m, 6 H) 3.09-3.17 (m, 1 H) 6.88 (dd, 1 H) 7.08 (dd, 2 H) 12.07-12.30 (broad, 1 H). 13C NMR (100 MHz, CHLOROFORM-d) δ ppm 16.91 (s, 1 C) 24.47 (s, 1 C) 25.70 (s, 1 C) 29.40 (s, 1 C) 30.84 (s, 1 C) 33.16 (s, 1 C) 35.32 (s, 1 C) 38.37 (s, 1 C) 64.80 (s, 1 C) 71.70 (s, 1 C) 126.13 (s, 1 C) 128.64 (s, 1 C) 128.93 (s, 1 C) 130.44 (s, 1 C) 132.44 (s, 1 C) 143.75 (s, 1 C). MS (M+1) 270.1, HPLC Purity 95% (AUC).

Workup

  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 (8 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)

Sources & evidence

ORD record
ord-5886f039400b42fabd1406fa7e4d92f0
Source dataset
uspto-grants-2012_03
Patent number
US08138377B2

Reaction notes

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