Triethylamine → (4-Nitrophenyl)methyl 3-hydroxyazetidine-1-carboxylate

A solution of 1-benzhydryl-3-hydroxyazetidine (9.00 g, 37.6 mmol) in methanol (270 ml) was subjected to catalytic hydrogenation in the presence of 10% palladium on charcoal (9.00 g) in a water bath (50° C.) for 5.5 hours. After checking the completion of the reaction, the reaction mixture was filtered in order to remove the catalyst and the filtrate concentrated under reduced pressure. The residue was partitioned between ethyl acetate and distilled water. The organic layer was concentrated under reduced pressure and dried in vacuo to give a crude product. To a solution of the crude product in a mixture of methylene chloride (82 ml) and methanol (55 ml) were added chloroformic acid p-nitrobenzyl ester (8.90 g, 41.3 mmol) and triethylamine (5.79 ml, 41.3 mmol) in an ice bath. The mixture was stirred at room temperature for 1.5 hours. After checking the completion of the reaction, the reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate solution. The obtained organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using n-hexane:ethyl acetate (1:1)→ethyl acetate as the eluant to afford 3-hydroxy-1-(p-nitrobenzyloxycarbonyl)azetidine (3.52 g, yield 37%) as pale yellow crystals.

1. customthe completion of the reaction
2. filtrationthe reaction mixture was filtered in order
3. customto remove the catalyst
4. concentrationthe filtrate concentrated under reduced pressure
5. customThe residue was partitioned between ethyl acetate
6. distillationdistilled water
7. concentrationThe organic layer was concentrated under reduced pressure
8. customdried in vacuo
9. customto give a crude product
10. customthe completion of the reaction
11. customthe reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate solution
12. washThe obtained organic layer was washed with saturated aqueous sodium chloride solution
13. dry with materialdried over anhydrous sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated under reduced pressure
16. customThe residue was purified by chromatography on a silica gel column

ORD record

ord-6c4b1259e3864d7bbc5142ef57dac2fa

Source dataset

uspto-grants-2006_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07001897B2