H-Dab(boc)-OH → (2S)-2-{[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)carbonyl]-amino}-4-[(tert-butoxycarbonyl)amino]butanoic acid

7.50 g (15.4 mmol) of the compound from example 1A was dissolved in 150 ml dichloromethane. 3.36 g (15.4 mmol) (2S)-2-Amino-4-[(tert-butoxycarbonyl)amino]butanoic acid was added. The reaction mixture was split into 10 portions. The portions were heated for 30 min in a sealed tube at 75° C. in a microwave synthesizer. The combined reaction mixture was extracted with approx. 100 ml saturated ammonium chloride solution. The aqueous phase was twice back extracted with approx. 50 ml dichloromethane each. The combined organic phases were extracted with approx. 50 ml brine and dried over sodium sulfate. The solvent was removed under reduced pressure. The raw product was dissolved in dichloromethane and chromatographed over approx. 1 l silica gel. Solvents used were dicloromethane/ethyl acetate 4/1, dichloromethane/methanol 10/1 to dichloromethane/methanol 1/1. The product-containing fractions were combined and concentrated to dryness under reduced pressure. This gave 8.70 g (10.8 mmol, 70% of theory) of the desired product.

1. customThe reaction mixture was split into 10 portions
2. customThe combined reaction mixture
3. extractionwas extracted with approx. 100 ml saturated ammonium chloride solution
4. extractionThe aqueous phase was twice back extracted with approx. 50 ml dichloromethane each
5. extractionThe combined organic phases were extracted with approx. 50 ml brine
6. dry with materialdried over sodium sulfate
7. customThe solvent was removed under reduced pressure
8. dissolutionThe raw product was dissolved in dichloromethane
9. customchromatographed over approx. 1 l silica gel
10. concentrationconcentrated to dryness under reduced pressure

ORD-Eintrag

ord-fcffd8e446b142c89500cc97bf508f5f

Quelldatensatz

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09315543B2