Acetic Acid → HCID 71739075, compound

Participants

Reaction Conditions

Reaction Steps

In a 100 pressure flask 2-(6-chloropyridin-3-yloxy)-2-methylpropanal (10 g, 50.1 mmol, Eq: 1.00), acetic acid (5.7 mL, 100 mmol) and sodium triacetoxyborohydride (22.3 g, 105 mmol, Eq: 2.1) were dissolved in dichloromethane (58 mL) and cooled to 0° C. To this solution was added azetidine (11.8 mL, 175 mmol, 3.5 equiv) via dropwise addition. The reaction was heated overnight at 55° C., then cooled to ambient temperature. The reaction mixture was diluted with 120 ml saturated NaHCO3 and 80 ml dichloromethane. Mixture was shaken and the dichloromethane layer collected. The organic layer was washed again with 100 ml of 5% NaHCO3 (aq) solution and with an equal volume of 50% diluted brine. The aqueous phase was back-extracted 2×70 ml dichlormethane. The combined organics were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by Analogix MPLC (SF25-60 gram column) eluted with 100% DCM to 5% MeOH/DCM gradient to afford a 70:30 mixture of the desired product: 2-(6-chloro-pyridin-3-yloxy)-2-methyl-propan-1-ol (7.5 g) as a pale yellow oil. Used as is in the next step.

Provenance & Evidence