Lithium hydroxide, monohydrate → (S)-1-((S)-2-(tert-butoxycarbonylamino)-3-methylbutanoyl)indoline-2-carboxylic acid

Lithium hydroxide monohydrate (187 mg, 4.46 mmol, Eq: 3) in water (4.5 mL) was added to an ice-bath cooled solution of (S)-ethyl 1-((S)-2-(tert-butoxycarbonylamino)-3-methylbutanoyl)indoline-2-carboxylate (0.58 g, 1.49 mmol, Eq: 1.00) in THF (13.5 mL) and MeOH (4.5 mL). The cooling bath was removed and the reaction was stirred at rt for 1 h. 0.1 M Aqueous KHSO4 (50 mL) was added to the reaction mixture and the resulting mixture was extracted with DCM (2×50 mL). The aqueous layer was further acidified with 1 M aqueous HCl (˜5 mL) and extracted again with DCM (2×50 mL). The organic layers were combined, dried over Na2SO4 and concentrated in vacuo. The residue was azeotroped with hexanes to give (S)-1-((S)-2-(tert-butoxycarbonylamino)-3-methylbutanoyl)indoline-2-carboxylic acid (0.56 g), m/z=363 (M+H).

1. customThe cooling bath was removed
2. addition0.1 M Aqueous KHSO4 (50 mL) was added to the reaction mixture
3. extractionthe resulting mixture was extracted with DCM (2×50 mL)
4. extractionextracted again with DCM (2×50 mL)
5. dry with materialdried over Na2SO4
6. concentrationconcentrated in vacuo
7. customThe residue was azeotroped with hexanes

ORD-Eintrag

ord-974bfb805e1246178784cd916f97e6fd

Quelldatensatz

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09403768B2