تفاعل #1726686

معادلة التفاعل

2A

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

Cs2CO3

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

→

3A

المردود 74.0%

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

المردود 74.0%

المذيبات

DMF

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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]−.

المصدر