1,2-Dichloroethane → tert-Butyl methylcarbamate

(S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-3-methyl-butyryl}-2,3-dihydro-1H-indole-2-carboxylic acid (60 mg, 134 μmol, Eq: 1) and EDC (77.1 mg, 402 μmol, Eq: 3) and HOAT (54.7 mg, 402 μmol, Eq: 3) were stirred in DMF (6 mL) for 10 min to give a light yellow solution. To this solution was added ammonium chloride (71.7 mg, 1.34 mmol, Eq: 10) and diisopropylethylamine (0.47 μL, 2.68 mmol, Eq: 20) in 2 mL of DMF. The mixture was stirred at rt overnight, and then concentrated in vacuo. The reaction mixture was poured into saturated aqueous NaHCO3 (30 mL) and extracted with DCM (2×20 mL). The organic layer was washed with 0.5 M aqueous citric acid and brine, and then concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 0% to 90% EtOAc in hexanes) to afford {(S)-1-[(S)-1-((S)-2-carbamoyl-2,3-dihydro-indole-1-carbonyl)-2-methyl-propylcarbamoyl]-ethyl})-methyl-carbamic acid tert-butyl ester as an off-white powder (39 mg), m/z=447 (M+H).

1. customto give a light yellow solution
2. concentrationconcentrated in vacuo
3. additionThe reaction mixture was poured into saturated aqueous NaHCO3 (30 mL)
4. extractionextracted with DCM (2×20 mL)
5. washThe organic layer was washed with 0.5 M aqueous citric acid and brine
6. concentrationconcentrated in vacuo
7. customThe crude material was purified by flash chromatography (silica gel, 0% to 90% EtOAc in hexanes)

ORD record

ord-bdc70c390dd5479398b1ae285b142b3b

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403768B2