Acetic Acid → HCID 71739075, compound

Temperature

0 °C

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.

1. additionvia dropwise addition
2. temperatureThe reaction was heated overnight at 55° C.
3. temperaturecooled to ambient temperature
4. customthe dichloromethane layer collected
5. washThe organic layer was washed again with 100 ml of 5% NaHCO3 (aq) solution and with an equal volume of 50% diluted brine
6. extractionThe aqueous phase was back-extracted 2×70 ml dichlormethane
7. dry with materialThe combined organics were dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe crude product was purified by Analogix MPLC (SF25-60 gram column)
11. washeluted with 100% DCM to 5% MeOH/DCM gradient
12. customto afford

ORD record

ord-fbcfb7617d4a45e3863ed3b47502a855

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889682B2