Tetrahydrofuran → Methyl 1-(((1(R)-(3-(((2-tetrahydropyranyl)oxy)methyl)phenyl)-3-(2-(1-hydroxy-1-methylethyl)phenyl)propyl)thio)methyl)cyclopropaneacetate

Participants

Reaction Conditions

Reaction Steps

The diol of Step 15 (17.9 g, 46.6 mmol) was dissolved in CH3CN (40 mL) and DMF (10 mL) and cooled to -42° C. under nitrogen. Diisopropylethylamine (8.5 mL, 48.9 mmol) was added followed by methanesulphonyl chloride (3.6 mL, 46.6 mmol) dropwise. The solution was stirred 1.5 hours with a mechanical stirrer while maintaining the temperature between -42° C. and -35° C.; then it was cooled to -45° C. The thiol of Step 10 (7.84 g, 48.9 mmol) was added followed by dropwise addition of DMF (15 mL). The potassium tert-butoxide in THF solution (56 mL, 1.75M, 97.9 mmol) was added to the reaction mixture within 20 minutes using a syringe pump. Stirring continued for 5 hours with slow warming from -35° C. to -22° C., giving a very thick translucid gel. The reaction was quenched with saturated aq. NH4Cl (250 mL) and EtOAc (300 mL). The product was extracted with EtOAc, washed with H2O and brine, and dried over MgSO4. Purification by flash chromatography (20% to 30% EtOAc in hexanes) gave 16.8 g (68%) of the title compound.

Provenance & Evidence