Hydrochloric Acid → methyl 2-[(2S)-2-{[(tert-butoxy)carbonyl]amino}-4-methylpentanamido]acetate

Dipeptide H-Leu-Gly-OCH3 : DIEA (21 mL) was added to a stirred solution of HCl.H-Gly-OCH3 (13 g) in EtOAc (500 mL). After 15 min, Boc-Leu-OH.H20 (20 g) and N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (25.5 g) were added in succession. The reaction mixture was stirred at room temperature for 18 h, and then filtered. The filtrate was washed serially with H20, 1N HCl, H20, 5% aqueous NaHCO3 and water. The dried (Na2SO4 +MgSO4) organic phase was concentrated to near dryness. Et20 was added to the concentrate and the mixture was stored at 4° C. for 18 h. The resultant precipitate was collected and dried to give Boc-Leu-Gly-OCH3 (15.6 g). The latter compound (15.5 g) was dissolved in CH2Cl2 (150 mL) and the solution cooled to 0° C. TFA (60 mL) was added dropwise to the cooled solution. The mixture was stirred at 0° C. for 1.5 h and then evaporated to dryness. TFA was removed from the residue by adding Dowex 1×2-400 ion exchange resin (40 g), prewashed with methanol (4×100 mL), 1N HCl (3×200 mL) and methanol (4×100 mL), to a solution of the crude residue in methanol (300 mL). (Note: Dowex is a trademark). The mixture was stirred at room temperature for 1h and then filtered. The filtrate was concentrated under reduced pressure to give TFA.H-Leu-Gly-OCH3 (17.9 g).

1. filtrationfiltered
2. washThe filtrate was washed serially with H20, 1N HCl, H20, 5% aqueous NaHCO3 and water
3. dry with materialThe dried (Na2SO4 +MgSO4) organic phase
4. concentrationwas concentrated
5. additionEt20 was added to the
6. concentrationconcentrate
7. waitthe mixture was stored at 4° C. for 18 h
8. customThe resultant precipitate was collected
9. customdried

ORD-Eintrag

ord-876ae74df9bb4495b10a0de960747bb6

Quelldatensatz

uspto-grants-1990_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US04891358