Réaction #333003

Équation de réaction

Boc-D-alanine

3,3-difluoroazetidine hydrochloride

HOBT

EDC

N,N-diisopropylethylamine

→

[(R)-2-(3,3-difluoro-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-carbamic acid tert-butyl ester

Rendement 91.3%

Solvants

DMF

Conditions de réaction

Traitement

1. 1
   Autrethen quenched with water
2. 2
   Extractionextracted with diethyl ether (2×)
3. 3
   LavageThe combined organic layers were washed twice with water and once with brine
4. 4
   Séchagethen dried over sodium sulfate
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated

Mode opératoire

A round-bottomed flask was charged with Boc-D-alanine (400 mg, 2.11 mmol), 3,3-difluoroazetidine hydrochloride (383 mg, 2.96 mmol), HOBT (356 mg, 2.33 mmol) and EDC (446 mg, 2.33 mmol). DMF (9 ml) was added followed by N,N-diisopropylethylamine (1.0 ml, 5.73 mmol). The reaction mixture was stirred at room temperature for 48 h then quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated to give 509 mg (91%) of [(R)-2-(3,3-difluoro-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-carbamic acid tert-butyl ester as a light yellow solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 5.14 (d, J=7.2 Hz, 1H), 4.59-4.80 (m, 1H), 4.17-4.55 (m, 4H), 1.45 (s, 9H), 1.32 (d, J=7.2 Hz, 3H).

Source