Iodine → tert-Butyl 3-(hydroxymethyl)azetidine-1-carboxylate

Temperature

0 °C

To a stirred mixture of 0.56 g (14.91 mmol) sodium borohydride in 10 mL THF was added 1.0 g (4.97 mmol) 1-(tert-butoxycarbonyl)-3-azetidinecarboxylic acid, and the reaction mixture was cooled to 0° C. 1.26 g (4.97 mmol) iodine in 5 mL THF was added dropwise over 15 minutes and the reaction was stirred at 0° C. for 10 minutes, then heated under reflux for 18 hours. The mixture was allowed to cool to room temperature, diluted with 80 mL MeOH and stirred until all effervescence ceased. After evaporation of the solvent, 25 mL 20% (w/w) KOH was added to the residue and the mixture was stirred for 4.5 hours. The mixture was extracted with DCM (3×100 mL) and the combined organic layers were dried over MgSO4. After filtration, the solvent was evaporated to give the desired product, which was used for the next step without further purification.

1. temperatureheated
2. temperatureunder reflux for 18 hours
3. temperatureto cool to room temperature
4. stirringstirred until all effervescence
5. customAfter evaporation of the solvent, 25 mL 20% (w/w) KOH
6. additionwas added to the residue
7. stirringthe mixture was stirred for 4.5 hours
8. extractionThe mixture was extracted with DCM (3×100 mL)
9. dry with materialthe combined organic layers were dried over MgSO4
10. filtrationAfter filtration
11. customthe solvent was evaporated

ORD record

ord-1feb6a6dacda415086fbae711ad4636b

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09346816B2