Lithium Hydroxide → (6S,9R,13S)-9-Benzyl-13-((E)-4-tritylsulfanyl-but-1-enyl)-6-tritylsulfanylmethyl-14-oxa-4,7,10,17-tetraaza-spiro[2.15]octadecane-5,8,11,15,18-pentaone

To a solution of 4 (305 mg, 0.29 mmol, 1 eq) in THF (10 mL) at 0° C. was added a solution of LiOH (10.3 mg, 0.43 mmol, 1.5 eq) in H2O (2 mL) dropwise. The mixture was stirred for 2 h, then quenched with 1N HCl (3 mL) and brine (10 mL). The organic layer was separated and the resulting aqueous layer was further extracted with EtOAc (2×15 mL) and (15 mL). The combined organic extracts were dried over MgSO4 and the solvent was removed in vacuo. The resulting carboxylic acid was then dried on the high-vacuum pump for 2 h. To a solution of MNBA (118 mg, 0.34 mmol, 1.2 eq) and DMAP (84 mg, 0.69 mmol, 2.4 eq) in CH2CL2 (200 mL) was added a solution of the crude carboxylic acid in CH2Cl2 (130 mL) and THF (20 mL) dropwise over 3 h. The reaction mixture was then left to stir up at rt overnight. The solvent was then removed in vacuo and the residue was further purified by silica gel column chromatography with hexane/EtOAc (1:9→0:1) to yield 5 as a white solid (171 mg, 58%).

1. customquenched with 1N HCl (3 mL) and brine (10 mL)
2. customThe organic layer was separated
3. extractionthe resulting aqueous layer was further extracted with EtOAc (2×15 mL) and (15 mL)
4. dry with materialThe combined organic extracts were dried over MgSO4
5. customthe solvent was removed in vacuo
6. dry with materialThe resulting carboxylic acid was then dried on the high-vacuum pump for 2 h
7. waitThe reaction mixture was then left
8. stirringto stir up at rt overnight
9. customThe solvent was then removed in vacuo
10. customthe residue was further purified by silica gel column chromatography with hexane/EtOAc (1:9→0:1)

ORD record

ord-30138c1eebfb4c539c974bb3026b3342

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08614193B2