Toluene → HCID 118062866, compound

A solution of Intermediate 246A (77 mg, 0.679 mmol), TEA (0.142 mL, 1.018 mmol) and DPPA (0.146 mL, 0.679 mmol) in toluene (5 mL) was stirred at 90° C. for 2 h. The reaction mixture was cooled to RT and to it was added a solution of Intermediate 185B (100 mg, 0.339 mmol) in THF (1 mL) and stirred at RT for 4 h. The reaction mixture was quenched with water and the aqueous layer was extracted with ethyl acetate (3×5 mL) The combined organic layer was washed with an aqueous solution of 10% aq. NaHCO3, water, dried over Na2SO4, filtered and the filtrate concentrated to afford the crude product as an off-white solid. The crude material was purified by preparative TLC. The crude material was loaded on a 0.5 mm silica gel plate and developed using 6% MeOH in CHCl3. The band containing the desired product was separated and extracted into 10% MeOH in DCM, filtered and the filtrate concentrated to afford a mixture cis and trans isomers as an off-white solid. The individual isomers were separated using preparative chiral SFC purification.

1. customThe reaction mixture was quenched with water
2. extractionthe aqueous layer was extracted with ethyl acetate (3×5 mL) The combined organic layer
3. washwas washed with an aqueous solution of 10% aq. NaHCO3, water
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationthe filtrate concentrated

ORD record

ord-47b0caac386246ccb551c2359d30fe27

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09273058B2