Pyridine → (S)-2-[(azepane-1-carbonyl)-amino]-4-methyl-pentanoic acid benzyl ester

Temperature

-10 °C

A solution of triphosgene (15.7 g, 52.9 mmol) in CH2Cl2 (600 mL) was cooled to −10° C. under a nitrogen atmosphere. The solution was treated dropwise with a solution of (S)-2-amino-4-methyl-pentanoic acid benzyl ester (28.1 g, 0.127 mol) and pyridine (26 mL, 0.32 mol) in 150 mL of CH2Cl2. The resulting solution was stirred at −10° C. for 90 minutes and then treated with a solution of hexamethyleneimine (22 mL, 0.38 mmol) in 75 mL of CH2Cl2. The resulting solution was stirred for 48 hours at room temperature. The reaction mixture was concentrated, and the residue was dissolved in ether and washed with 1N HCl solution, water, and saturated aqueous CuSO4 solution. The organic layer was dried (Mg2SO4), treated with activated charcoal, and filtered. The filtrate was concentrated to approximately ½ volume and treated with hexane. The resulting suspension was stored overnight at −10° C. The solid was collected by filtration, washed with hexane, and dried under vacuum to give (S)-2-[(azepane-1-carbonyl)-amino]-4-methyl-pentanoic acid benzyl ester as a white solid (38.6 g, 88%); mp 87-88° C.

1. stirringThe resulting solution was stirred for 48 hours at room temperature
2. concentrationThe reaction mixture was concentrated
3. dissolutionthe residue was dissolved in ether
4. washwashed with 1N HCl solution, water, and saturated aqueous CuSO4 solution
5. dry with materialThe organic layer was dried (Mg2SO4)
6. additiontreated with activated charcoal
7. filtrationfiltered
8. concentrationThe filtrate was concentrated to approximately ½ volume
9. additiontreated with hexane
10. waitThe resulting suspension was stored overnight at −10° C
11. filtrationThe solid was collected by filtration
12. washwashed with hexane
13. customdried under vacuum

ORD record

ord-b9635923ef63475b8504e517f3a07cf6

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06362174B1