HCID 57989172, compound → HCID 86636757, compound

Participants

Reaction Steps

4-(2-(1,3-Dioxolan-2-yl)ethylthio)butan-1-ol (example 281, step a) (500 mg) was dissolved in an 80% solution of aqueous formic acid (6 mL) and the reaction mixture was stirred at room temperature over the weekend. The mixture was diluted with water (10 mL) and extracted with ether (3×10 mL) then the organics were washed with brine (10 mL), dried over sodium sulphate, filtered and evaporated to afford 3-(4-hydroxy-butylsulfanyl)-propionaldehyde as an oil. This was dissolved in dry methanol and (2-isopropyl-thiazol-4-yl)-(1-oxa-4,9-diaza-spiro[5.5]undec-4-yl)-methanone trifluoroacetate (Example 22, step b) (606 mg) and 3 Å molecular sieves were added. Acetic acid (0.2 mL) was added and the mixture stirred for 5 minutes under argon before cooling to 0° C. and addition of sodium triacetoxyborohydride (633 mg). The cooling bath was removed and the reaction mixture stirred at room temperature overnight. The mixture was filtered then applied directly to an SCX-2 cartridge and washed with methanol before eluting the product with 2N ammonia in methanol. Further purification was by silica gel chromatography eluting with 10% methanol in DCM to afford the subtitled compound as a pale green oil. Yield 0.37 g.

Provenance & Evidence