Sodium triacetoxyborohydride → [1-(2-Amino-3-methylbutyl)piperidin-4-yl]-(3,4-dichlorophenyl)methanone

A mixture of 4-(3,4-dichlorobenzoyl)piperidine (1.28 g, 4.96 mmol) (see., Boswell et. al., J. Med. Chem., 21, 136, (1977)) and DL-N-BOC-Valinal (1.33 g, 6.6 mmol) (see., Stanfield et. al., J. Org. Chem., 46(23), 4797, (1981)) in dichloromethane (150 mL) was treated with sodium triacetoxyborohydride (1.36 g, 6.4 mmol). The reaction mixture was stirred under nitrogen for 1 day, then directly purified by filtration through a pad of silica gel by elution with hexanes and ethyl acetate. The organics were removed and the resultant oil (2.1 g) was dissolved in dichloromethane (22 mL) and treated with trifluoroacetic acid (8 mL). After stirring under nitrogen for 1 h, the solvent was removed in vacuo. The residue was treated with aqueous sodium bicarbonate until basic and the product was extracted into chloroform. The organic layer was dried with magnesium sulfate, filtered and concentrated to give [1-(2-amino-3-methylbutyl)piperidin-4-yl]-(3,4-dichlorophenyl)methanone (1.47 g) as an oil.

1. filtrationdirectly purified by filtration through a pad of silica gel by elution with hexanes and ethyl acetate
2. customThe organics were removed
3. dissolutionthe resultant oil (2.1 g) was dissolved in dichloromethane (22 mL)
4. additiontreated with trifluoroacetic acid (8 mL)
5. stirringAfter stirring under nitrogen for 1 h
6. customthe solvent was removed in vacuo
7. additionThe residue was treated with aqueous sodium bicarbonate until basic and the product
8. extractionwas extracted into chloroform
9. dry with materialThe organic layer was dried with magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated

ORD record

ord-f4fe847f17de4f3a9da9eec297eb4dd5

Source dataset

uspto-grants-2000_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06140344