Hydrochloric Acid → Ether hydrochloride

HRID 1096743Notes

Reaction equation

HRID 1096743 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]12[CH2:16][CH:15]1[C:14](=O)[CH2:13][CH2:12]2.[CH3:18][NH:19][CH3:20].[C:21]([BH3-])#N.[Na+].[ClH:25].[CH3:26][OH:27]>>[ClH:25].[CH3:18][N:19]([CH3:20])[CH:14]1[CH2:13][CH2:12][C:11]2([C:2]3[CH:3]=[CH:4][C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[CH:1]=3)[CH:15]1[CH2:16]2.[ClH:25].[CH2:26]([O:27][CH2:1][CH3:2])[CH3:21]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 674DimethylamineHCID 887MethanolHCID 5003444Sodium cyanoborohydrideHCID 597791645-(Naphthalen-2-yl)bicyclo[3.1.0]hexan-2-one

Product 2

HCID 10953452Ether hydrochlorideHCID 66781280N,N-dimethyl-5-(naphthalen-2-yl)bicyclo[3.1.0]hexan-2-amine hydrochloride

Procedure

To a solution of 5-(naphthalen-2-yl)bicyclo[3.1.0]hexan-2-one (0.72 g, 3.24 mmol) in methanol (50 mL) was added dimethylamine (2M in tetrahydrofuran; 6.48 mL, 12.96 mmol, 4 eq.) and sodium cyanoborohydride (0.26 g, 4.21 mmol, 1.3 eq). The mixture was stirred at room temperature overnight. The reaction mixture was cooled to 10° C., and acidified with 1N HCl (25 mL). The reaction mixture was concentrated at 30° C. and the resulting aqueous layer diluted with water (25 mL). The aqueous layer was then extracted with ethyl acetate (125 mL) to remove nonpolar impurities. The aqueous layer was then adjusted to pH 9 with 1N NaOH (25 mL), and the aqueous layer extracted with ethyl acetate (3×25 mL). The combined organic layers were dried over magnesium sulphate, filtered and concentrated in vacuo. The residue was then dissolved in diethyl ether (20 mL) and the HCl salt was formed by slowly adding HCl/diethyl ether solution (10 mL). The slurry was stirred for 30 mins before filtration. The solids were rinsed with ice cold diethyl ether (10 mL) and the compound was quickly transferred to a vacuum oven and dried for 12 hours to afford the desired compound (0.81 g, 28%) as a white solid. 1H NMR (400 MHz, CD3OD) δ ppm 1.18-1.21 (1H, m, CH), 1.43-1.46 (1H, m, CH), 1.57-1.61 (1H, m, CH), 2.14-2.19 (1H, m, CH), 2.27-2.36 (2H, m, CH2), 2.37-2.43 (1H, m, CH), 2.92 (3H, s, CH3), 3.06 (3H, s, CH3), 4.04-4.09 (1H, m, CH), 7.34 (1H, dd, J=1.9, 8.4, ArH), 7.39-7.47 (2H, m, ArH), 7.71-7.72 (1H, m, ArH), 7.79-7.80 (3H, m, ArH). 13C NMR (400 MHz, CD3OD); δ ppm 13.74 (s, 1C), 24.28 (s, 1C), 25.31 (s, 1C), 30.70 (s, 1C), 33.53 (s, 1C), 41.58 (s, 1C), 41.89 (s, 1C), 69.80 (s, 1C), 124.50 (s, 1C), 124.75 (s, 1C), 125.33 (s, 1C), 125.93 (s, 1C), 127.25 (s, 1C), 127.87 (s, 1C), 132.35 (s, 1C), 133.57 (s, 1C), 140.02 (s, 1C). LCMS (M+1) 252.

Workup

  1. temperatureThe reaction mixture was cooled to 10° C.
  2. concentrationThe reaction mixture was concentrated at 30° C.
  3. additionthe resulting aqueous layer diluted with water (25 mL)
  4. extractionThe aqueous layer was then extracted with ethyl acetate (125 mL)
  5. customto remove nonpolar impurities
  6. extractionthe aqueous layer extracted with ethyl acetate (3×25 mL)
  7. dry with materialThe combined organic layers were dried over magnesium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. dissolutionThe residue was then dissolved in diethyl ether (20 mL)

Sources & evidence

ORD record
ord-1b4bd7b531f24ae3bdd121dbf06e2d40
Source dataset
uspto-grants-2012_03
Patent number
US08138377B2

Reaction notes

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