7-Benzyl-3-thia-7-azabicyclo[3.3.1]nonane → 3-Thia-7-azabicyclo[3.3.1]nonane

A 50-mL, three-necked, round-bottomed flask was equipped with a magnetic stirrer, a heating mantle, a standard condenser with a N2 inlet and two glass stoppers. In one portion, anhydrous HCO2NH4 (1.11 g, 17.1 mmol) was added under N2 to a mixture of the amine (27, 0.90 g, 3.86 mmol) and 10% Pd/C (0.90 g) in anhydrous CH3OH (25 mL). With stirring, the mixture was brought to reflux for 30 min, filtered through a Celite pad on a fritted funnel (which was washed thoroughly with CH2Cl2), and then concentrated to give a gummy oil with suspended solid. This material was again dissolved in CH2Cl2 (~15 mL), and the suspension was filtered to remove any unreacted ammonium formate. The filtrate was then concentrated to near saturation and placed in a diffusion chamber of ether overnight. Crude amine (28) became an oil; however, the mother liquor, containing predominantly starting material, could be decanted. Chromatography of the oil employed a gradient elution of CH3OH/CH2Cl2 (300 mL of 10% CH3OH/CH2Cl2, 50 mL of 20% CH3OH/CH2Cl2, 100 mL of 50% CH3OH/CH2Cl2, and 100 mL of CH3OH) on silica gel (35 g, 1.5 cm×62 cm) and afforded 0.32 g (56.9%) of amine (28) (Rf =0.11, 10% CH3OH/CH2Cl2) as a light, gummy solid which was used without further purification. 1H NMR (DCCl3) δ1.84, 2.04 [two bd, 2H, H(9)], 2.31 [bs, 2H, H(1,5)], 2.80 [bd, 2H, H(2,4)ax, J=12.3 Hz], 3.20 [bd, 2H, H(2,4)eq, J=13.7 Hz], 3.45 [m, 2H, H(6,8)ax ], 3.73 [bd, 2H, H(6,8)eq, J=13.2 Hz], 7.59 (bs, 1H, N-H); 13C NMR (DCCl3) ppm 24.88 [d, C(1,5)], 29.79 [t, C(9)], 32.17 [t, C(2,4)], 47.8 [t, C(6,8)].

1. customA 50-mL, three-necked, round-bottomed flask was equipped with a magnetic stirrer
2. temperatureto reflux for 30 min
3. filtrationfiltered through a Celite pad on a fritted funnel (which
4. washwas washed thoroughly with CH2Cl2), and
5. concentrationthen concentrated
6. customto give a gummy oil
7. filtrationthe suspension was filtered
8. customto remove any unreacted ammonium formate
9. concentrationThe filtrate was then concentrated
10. customplaced in a diffusion chamber of ether overnight
11. additionhowever, the mother liquor, containing predominantly starting material
12. customcould be decanted
13. washa gradient elution of CH3OH/CH2Cl2 (300 mL of 10% CH3OH/CH2Cl2, 50 mL of 20% CH3OH/CH2Cl2, 100 mL of 50% CH3OH/CH2Cl2, and 100 mL of CH3OH) on silica gel (35 g, 1.5 cm×62 cm)

ORD record

ord-b64de3c74d7d434ca0ca4debb928fe58

Source dataset

uspto-grants-1992_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05110933