反应 #1726686

反应方程式

2A

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

Cs2CO3

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

→

3A

收率 74.0%

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

收率 74.0%

溶剂

DMF

反应条件

后处理

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

实验过程

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]−.

来源