Réaction #303903

Équation de réaction

3-Methanesulfonyloxy-azetidine-1-carboxylic acid tert-butyl ester

NaH

4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole

→

title compound

3-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-azetidine-1-carboxylic acid tert-butyl ester

Solvants

DMF

DMF

Conditions de réaction

Traitement

1. 1
   Autreto warn to RT
2. 2
   workup.ADDITIONAfter complete addition
3. 3
   Températurethe reaction mixture is heated at 95° C. for 5 h
4. 4
   AutreThe reaction is quenched with water
5. 5
   Extractionextracted with EtOAc several times
6. 6
   LavageThe combined organic layers are washed with brine
7. 7
   Séchagedried over Na2SO4
8. 8
   Filtrationfiltered
9. 9
   Concentrationthe filtrate is concentrated in vacuo
10. 10
    AutreThe residue is purified by chromatography on a 40 g silica gel column on a Combiflash Companion™ (Isco Inc.) apparatus (gradient CH2Cl2: TBDME from 1:0=>0:1)

Mode opératoire

NaH (60% in mineral oil, 222 mg, 5.6 mmol) is added portionwise to a stirred solution of 4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (1.10 g, 5.56 mmol) in DMF (20 ml). The resulting mixture is stirred for 1 h at 0° C. and then allowed to warn to RT. A solution of 3-Methanesulfonyloxy-azetidine-1-carboxylic acid tert-butyl ester (as obtained in preparation 80, 1.39 g, 5.56 mmol) in DMF (3 ml) is then added dropwise. After complete addition, the reaction mixture is heated at 95° C. for 5 h. The reaction is quenched with water and extracted with EtOAc several times. The combined organic layers are washed with brine, dried over Na2SO4, filtered and the filtrate is concentrated in vacuo. The residue is purified by chromatography on a 40 g silica gel column on a Combiflash Companion™ (Isco Inc.) apparatus (gradient CH2Cl2: TBDME from 1:0=>0:1) to afford the title compound as a colorless foam, Rt=1.200 min (Acquity HPLC BEH C18, 2.1×50 mm, 1.7 micron, detection 215 nM, 0.1 min 2% CH3CN in H2O, 2% to 100% CH3CN in H2O in 1.5 min, 0.4 min 100% CH3CN+0.1% TFA, flow rate 1.0 ml/min); MS: 350 (M+1)+.

Source