1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-3-(Naphthalen-2-ylmethyl)piperazin-2-one

(2R)-2-(2-naphthyl)methyl-3-oxo-4-phenethylpiperazine-1-carboxylic acid tert-butyl ester (1.2 g; 2.7 mmol) was dissolved in a mixture of TFA (5 ml) and methylene chloride (5 ml) and stirred for 15 min. Methylene chloride (30 ml) and aqueous sodium hydrogencarbonate (saturated) was added to pH 8. The mixture was extracted with methylene chloride (3×10 ml) and the combined aqueous phases were dried (magnesium sulphate) and the solvent was removed in vacuo. Part of the residue (400 mg 1.2 mmol) were added to a mixture of (2E)-5-(tert-butoxycarbonylamino)-5-methylhex-2-enoic acid (282 mg; 1.2 mmol); HOAt (158 mg; 1.2 mmol), EDAC (245 mg; 1.3 mmol) and DIEA (150 mg; 1.2 mmol) and stirred overnight. Methylene chloride (50 ml) was added and the mixture was washed with aqueous sodium hydrogensulphate (10%; 50 ml); aqueous sodium hydrogencarbonate (saturated; 50 ml) and water (50 ml). The organic phase was dried (magnesium sulphate) and the solvent removed in vacuo. The residue was chromatographed on silica (2×20 cm) and the residue was dissolved in a mixture of TFA (2 ml) and methylene chloride (2 ml) and stirred for 5 min. Methylene chloride and an aqueous solution of sodium hydrogenarbonate (sat.) was added to pH 8. The mixture was extracted with methylene chloride (2×10 ml). The organic phase was dried (magnesium sulphate) and the solvent was removed in vacuo to afford 310 mg of the title compound.

1. extractionThe mixture was extracted with methylene chloride (3×10 ml)
2. dry with materialthe combined aqueous phases were dried (magnesium sulphate)
3. customthe solvent was removed in vacuo
4. washthe mixture was washed with aqueous sodium hydrogensulphate (10%; 50 ml)
5. dry with materialThe organic phase was dried (magnesium sulphate)
6. customthe solvent removed in vacuo
7. customThe residue was chromatographed on silica (2×20 cm)
8. dissolutionthe residue was dissolved in a mixture of TFA (2 ml) and methylene chloride (2 ml)
9. stirringstirred for 5 min
10. additionMethylene chloride and an aqueous solution of sodium hydrogenarbonate (sat.) was added to pH 8
11. extractionThe mixture was extracted with methylene chloride (2×10 ml)
12. dry with materialThe organic phase was dried (magnesium sulphate)
13. customthe solvent was removed in vacuo

ORDレコード

ord-d4640e8f09014896899b1adbbe661c66

出典データセット

uspto-grants-1999_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05922770