Diisopropylethylamine → HCID 59875636, compound

3-(tert-Butoxycarbonylaminomethyl)benzoic acid (407 mg) was dissolved in dichloromethane (6 ml) and then converted to the symmetrical anhydride by stirring with N-ethyl-N'-(3-dimethylaminopropyl)-carbodiimide hydrochloride (155 mg) for 10 min. A solution of (3E,5R)-5-amino-2-benzyl-6-(2-naphthyl)hex-3-en-1-ol hydrochloride (149 mg) and N,N-diisopropylethylamine (70 μl) in dichloromethane (3 ml) was added to the mixture and then reacted for 20 h at 20° C. The reaction mixture was then concentrated to an oil and redissolved in ethyl acetate (50 ml). The solution was extracted successively with 5% aqueous sodium hydrogen carbonate (100 ml) and with water (2×100 ml). The combined organic phases were dried (sodium sulfate) and concentrated in vacuo to an oil. The oil was dissolved in dichloromethane/trifluoroacetic acid 1:1 (6 ml) and stirred. After 10 min the mixture was concentrated by a stream of nitrogen and the resulting oil was redissolved in acetic acid (1 ml). Then water (40 ml) and acetonitrile (12 ml) were added. The solution of crude product of the title compound was then purified by semipreparative HPLC in five runs on a 25 mm×250 mm column packed with 7μ C-18 silica. The column was preequilibrated with 30% acetonitrile in 0.05M ammonium sulfate, and was adjusted to pH 2.5 with 4M sulfuric acid.

1. customreacted for 20 h at 20° C
2. concentrationThe reaction mixture was then concentrated to an oil
3. dissolutionredissolved in ethyl acetate (50 ml)
4. extractionThe solution was extracted successively with 5% aqueous sodium hydrogen carbonate (100 ml) and with water (2×100 ml)
5. dry with materialThe combined organic phases were dried (sodium sulfate)
6. concentrationconcentrated in vacuo to an oil
7. dissolutionThe oil was dissolved in dichloromethane/trifluoroacetic acid 1:1 (6 ml)
8. concentrationAfter 10 min the mixture was concentrated by a stream of nitrogen
9. dissolutionthe resulting oil was redissolved in acetic acid (1 ml)
10. additionThen water (40 ml) and acetonitrile (12 ml) were added
11. customThe solution of crude product of the title compound was then purified by semipreparative HPLC in five runs on a 25 mm×250 mm column

ORD record

ord-0055c7b73b6d44e89fb7a4b34afe0827

Source dataset

uspto-grants-2000_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06013658