Hydrochloric Acid → 8-Benzyl-8-azabicyclo(3.2.1)octan-3-one
Reaction equation
[CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:9](=O)[CH2:10][CH2:11][CH:12]=[O:13].[CH2:15]([C:22](O)=O)[C:16](CC(O)=O)=O.O.O.O.C([O-])(=O)C.[Na+].Cl>O>[CH2:1]([N:8]1[CH:10]2[CH2:9][CH2:22][CH:15]1[CH2:16][C:12](=[O:13])[CH2:11]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1Participants
Conditions
- Temperature
- 50 °C
Procedure
Under N2, a solution of benzylamine (36.1 ml, 0.33 mol) in water (435 ml) was added within 45 min at 3 to 8° C. to a solution of 1,4-butane dialdehyde (1.15 equiv.), 1,3-acetone dicarboxylic acid (1.5 equiv.) and sodium acetate trihydrate (2 equiv.) in 330 ml water as described in Example 1, Step (a). The mixture was warmed up to 50° C. over 5 h and kept at this temperature for 2 h. After cooling to 20-25° C., 80 ml conc. HCl was added and the solution was washed with TBME (2×240 ml). The pH of the aqueous phase was adjusted to 7-8 with NaOH and the product layer was separated. The aqueous phase was extracted with TBME (3× with a total of 240 ml). The combined product phases were dried over Na2SO4 and concentrated as completely as possible under vacuum at 50°. Yield: 68.7 g (90% abs.). Assay (HPLC): 93% pure vs. standard.
Workup
- temperatureAfter cooling to 20-25° C.
- washthe solution was washed with TBME (2×240 ml)
- customthe product layer was separated
- extractionThe aqueous phase was extracted with TBME (3× with a total of 240 ml)
- dry with materialThe combined product phases were dried over Na2SO4
- concentrationconcentrated as completely as possible under vacuum at 50°
Sources & evidence
- ORD record
- ord-27350671acb148a8b54ca271aad59fa3
- Source dataset
- uspto-grants-2008_12
- Patent number
- US07459556B2
Reaction notes
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