Gamma-Aminobutyric Acid → Methyl 4-{[(benzyloxy)carbonyl]amino}butanoate

Temperature

2.5 °C

4-Aminobutyric acid (7.5 g) was dissolved in a mixture of tetrahydrofuran (80 ml) and water (80 ml), which was cooled at 0 to 5° C. in an ice bath. To a resulting mixture was added dropwise benzyloxycarbonyl chloride (10.4 ml) with maintaining the pH from pH 8.0 to 9.0 with 30% aqueous sodium hydroxide solution at 0 to 5° C. The reaction mixture was washed with ethyl acetate (300 ml) and aqueous layer was separated, which was adjusted to pH 1.0 with 6N-aqueous hydrochloric acid and extracted with ethyl acetate (300 ml). Organic layer was separated, washed with brine (100 ml×2) and dried over magnesium sulfate. Evaporation of the solvent gave a residue, which was dissolved in methanol (200 ml) and added conc. sulfic acid (1 ml). The resulting solution was refluxed for 3 hours. Evaporation of the solvent gave a residue, which was dissolved In ethyl acetate (300 ml), washed in turn with water (100 ml), saturated sodium hydrogen carbonate in water (100 ml×3) and brine (100 ml×2), and dried over magnesium sulfate. Solvent was removed under reduced pressure to give methyl 4-(benzyloxycarbonylamino)butyrate (14.65 g).

1. washThe reaction mixture was washed with ethyl acetate (300 ml) and aqueous layer
2. customwas separated
3. extractionextracted with ethyl acetate (300 ml)
4. customOrganic layer was separated
5. washwashed with brine (100 ml×2)
6. dry with materialdried over magnesium sulfate
7. customEvaporation of the solvent
8. customgave a residue, which
9. temperatureThe resulting solution was refluxed for 3 hours
10. customEvaporation of the solvent
11. customgave a residue, which
12. washwashed in turn with water (100 ml), saturated sodium hydrogen carbonate in water (100 ml×3) and brine (100 ml×2)
13. dry with materialdried over magnesium sulfate
14. customSolvent was removed under reduced pressure

ORD record

ord-ba0d0b85f1204568afd2301c69add566

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06355640B1