Réaction #1726686

Équation de réaction

2A

4-(2-Oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenol

Cs2CO3

tert-butyl 3-(methylsulfonyloxy)azetidine-1-carboxylate

→

3A

Rendement 74.0%

tert-Butyl 3-(4-(2-oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenoxy)azetidine-1-carboxylate

Rendement 74.0%

Solvants

DMF

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGThe reaction mixture was thereafter stirred at 90° C. for 24 h
2. 2
   FiltrationThe mixture was filtered
3. 3
   Autrethe solvent was evaporated
4. 4
   workup.DISSOLUTIONThe residue was dissolved in DMSO (6 mL)
5. 5
   Autrepurified by preparative RP HPLC (gradient: 15-55% acetonitrile over 30 min, 0.2% ammonia buffer)
6. 6
   Concentrationconcentrated
7. 7
   workup.ADDITIONDichloromethane was added
8. 8
   Autrethe solution was dried (phase separator)
9. 9
   Concentrationconcentrated

Mode opératoire

2A (0.77 g, 3.75 mmol) was dissolved in dry DMF (20 mL) and Cs2CO3 (2.44 g, 7.50 mmol) was added. The reaction mixture was stirred at room temperature for 10 min and then tert-butyl 3-(methylsulfonyloxy)azetidine-1-carboxylate (1.88 g, 7.50 mmol) was added. The reaction mixture was thereafter stirred at 90° C. for 24 h. The mixture was filtered and the solvent was evaporated. The residue was dissolved in DMSO (6 mL) and purified by preparative RP HPLC (gradient: 15-55% acetonitrile over 30 min, 0.2% ammonia buffer). The pure fractions were combined and concentrated. Dichloromethane was added and the solution was dried (phase separator) and concentrated. There was obtained 1.00 g (74%) of 3A as an oil which solidified on standing at room temperature. 1H NMR (500 MHz, CDCl3): δ 1.45 (s, 9H), 3.34 (s, 4H), 3.46 (s, 2H), 3.99 (dd, 2H), 4.28 (dd, 2H), 4.73 (s, 4H), 4.84 (m, 1H), 6.68 (d, 2H), 7.15 (d, 2H), MS (APCI+) m/z 361 [M+H]−.

Source