Ammonia → tert-Butyl 3-carbamoylazetidine-1-carboxylate

Temperature

-20 °C

To 1.0 g (4.97 mmol) boc-azetidine-3-carboxylic acid in 10 mL anhydrous THF was added 0.55 mL of 1-methyl-2-pyrrolidinone. The reaction mixture was cooled to −20° C., then 0.62 mL (4.72 mmol) isobutyl chloroformate was added and the reaction was stirred for 5 minutes. 1.51 mL (24.85 mmol) aqueous ammonia (28% w/w) was added and the mixture was stirred at −20° C. for 2 hours. 5 mL aqueous NaHCO3 (1 M) was added and the mixture was allowed to reach room temperature over 1 hour. The mixture was extracted with DCM (3×10 mL), the organic layers were combined, washed with aqueous NaHCO3 (1 M), aqueous citric acid (1 M) and dried over Na2SO4. After filtration and evaporation of the solvent the product was used in the next step without further purification.

1. stirringthe mixture was stirred at −20° C. for 2 hours
2. waitto reach room temperature over 1 hour
3. extractionThe mixture was extracted with DCM (3×10 mL)
4. washwashed with aqueous NaHCO3 (1 M), aqueous citric acid (1 M)
5. dry with materialdried over Na2SO4
6. filtrationAfter filtration and evaporation of the solvent the product
7. customwas used in the next step without further purification

ORD record

ord-b8b62807859a45e0b0529ee67bc96741

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09346816B2