Acetyl chloride → Isohexane ethyl acetate

Acetyl chloride (0.3 mL) was added dropwise to an ice-cooled solution of compound 7-3 (103.4 mg, 0.316 mmol) (see reference example 7) in methanol (2.9 mL). The solution was stirred at rt overnight, and then concentrated in vacuo, coevaporated twice with CH2Cl2, and dried under vacuum. Boc-L-leucine-H2O (96.2 mg, 0.386 mmol) and HATU (143 mg, 0.376 mmol) were added and the mixture was cooled in an ice bath. DMF (3.2 mL), followed by DIEA (220 μL, 1.26 mmol) were added. The resulting solution was stirred at rt for 6 h. The reaction mixture was concentrated in vacuo, redissolved in EtOAc (15 mL), and washed successively with saturated aqueous NaHCO3 (10 mL) and saturated aqueous NaCl (10 mL). The organic phase was dried (Na2SO4) and then concentrated in vacuo to give the crude material. Flash column chromatography (silica, 2/1 isohexane-EtOAc) gave compound 4i as white solids (127.8 mg, 92% yield).

1. concentrationconcentrated in vacuo
2. customdried under vacuum
3. temperaturethe mixture was cooled in an ice bath
4. additionwere added
5. stirringThe resulting solution was stirred at rt for 6 h
6. concentrationThe reaction mixture was concentrated in vacuo
7. dissolutionredissolved in EtOAc (15 mL)
8. washwashed successively with saturated aqueous NaHCO3 (10 mL) and saturated aqueous NaCl (10 mL)
9. dry with materialThe organic phase was dried (Na2SO4)
10. concentrationconcentrated in vacuo
11. customto give the crude material

ORD record

ord-10285fcff97745ed8a9410f811104d93

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426421B2