Methanol → tert-Butyl 3-oxo-1,4-diazepane-1-carboxylate

To a solution of methyl N-(3-aminopropyl)-N-(tert-butoxycarbonyl)glycinate (10.2 g) in tetrahydrofuran (THP)/methanol (2/1, 300 mL) was added 1M aqueous lithium hydroxide solution (60 mL). The resultant mixture was stirred at room temperature overnight. An additional 20 ML of 1M aqueous lithium hydroxide solution was added and the mixture was stirred for 6 h. Solvent was removed under reduced pressure, and the residue was dissolved in 50 mL of methanol and 200 mL of toluene and concentrated in vacuo. To the residue in dichloromethane (300 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC, 9.6 g) and 1-hydroxybenzotriazole (HOBT, 6.8 g). The mixture was stirred at room temperature for three days, then treated with saturated aqueous ammonium chloride solution and extracted with three portions of ethyl acetate. The combined organics were washed with brine, dried over sodium sulfate and concentrated. The residue was purified by chromatography (silica gel, eluting with 4 to 5% [10:1 methanol/aqueous ammonium hydroxide] in dichloromethane) to yield the title compound. MS 215.0 (M+1).

1. customSolvent was removed under reduced pressure
2. dissolutionthe residue was dissolved in 50 mL of methanol
3. concentration200 mL of toluene and concentrated in vacuo
4. additionTo the residue in dichloromethane (300 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC, 9.6 g) and 1-hydroxybenzotriazole (HOBT, 6.8 g)
5. stirringThe mixture was stirred at room temperature for three days
6. additiontreated with saturated aqueous ammonium chloride solution
7. extractionextracted with three portions of ethyl acetate
8. washThe combined organics were washed with brine
9. dry with materialdried over sodium sulfate
10. concentrationconcentrated
11. customThe residue was purified by chromatography (silica gel, eluting with 4 to 5% [10:1 methanol/aqueous ammonium hydroxide] in dichloromethane)

ORDレコード

ord-55a9dc4f489346cb9d8d4d1d0a3b4af6

出典データセット

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07560455B2