2-Chloro-N,N-dimethylethylamine → 4-(2-Dimethylaminoethyl)-[1,4]diazepane-1-carboxylic acid benzyl ester

Temperatur

70 °C

After adding N,N-dimethylformamide (20 ml) to [1,4]diazepane-1-carboxylic acid benzyl ester (2 ml) under a nitrogen atmosphere, potassium carbonate (6.67 g) and 2-dimethylaminoethyl chloride (1.67 g) were added at room temperature. The reaction mixture was heated to 70° C. and stirred for 2 hours. It was then heated to 80° C. and stirred for 1 hour. Next, 2-dimethylaminoethyl chloride (420 mg) was further added and the reaction mixture was stirred for 2 hours. The reaction mixture was then cooled to room temperature. It was subsequently partitioned between ethyl acetate (100 ml) and saturated aqueous ammonium chloride (50 ml). The separated organic layer was washed with saturated aqueous ammonium chloride (50 ml), water (50 ml) and brine (50 ml) in that order and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then the resultant residue was purified by silica gel column chromatography (FUJI SILYSIA NH, eluent; heptane:ethyl acetate=4:1). Fractions containing the target compound were concentrated under reduced pressure to provide a crude product of 4-(2-dimethylaminoethyl)-[1,4]diazepane-1-carboxylic acid benzyl ester (724 mg, 24.5%) as a pale yellow oil.

1. temperatureIt was then heated to 80° C.
2. stirringstirred for 1 hour
3. stirringthe reaction mixture was stirred for 2 hours
4. temperatureThe reaction mixture was then cooled to room temperature
5. customIt was subsequently partitioned between ethyl acetate (100 ml) and saturated aqueous ammonium chloride (50 ml)
6. washThe separated organic layer was washed with saturated aqueous ammonium chloride (50 ml), water (50 ml) and brine (50 ml) in that order
7. dry with materialdried over anhydrous sodium sulfate
8. distillationThe solvent was distilled off under reduced pressure
9. customthe resultant residue was purified by silica gel column chromatography (FUJI SILYSIA NH, eluent; heptane:ethyl acetate=4:1)
10. additionFractions containing the target compound
11. concentrationwere concentrated under reduced pressure

ORD-Eintrag

ord-2153047855524b2f92da7512d24ae4c1

Quelldatensatz

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07531532B2