Реакция #1726686

Уравнение реакции

2A

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

Cs2CO3

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

→

3A

Выход 74.0%

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

Выход 74.0%

Растворители

DMF

Условия реакции

Обработка

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

Методика

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]−.

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