Reacción #307924

Ecuación de reacción

(2S,4R)—N-Boc-4-fluoropyrrolidine-2-carboxylic acid

NaF

2,2-difluoro-1,3-dimethylimidazolidine

→

(2S,4R)—N-Boc-4-fluoropyrrolidine-2-carbonyl fluoride

Rendimiento 90.1%

Disolventes

dichloromethane

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaIt was cooled with ice
2. 2
   Otrothe ice bath was removed
3. 3
   workup.STIRRINGstirring
4. 4
   workup.WAITwas continued at room temperature for 20 minutes
5. 5
   OtroAll the volatiles were removed at reduced pressure
6. 6
   workup.ADDITIONthe obtained viscous liquid was mixed with 50 ml of pentane
7. 7
   Lavadowashed with water (50 ml×2)
8. 8
   SecadoThe organic layer was dried over anhydrous magnesium sulfate
9. 9
   Filtraciónfiltered
10. 10
    OtroRemoval of solvent at reduced pressure

Procedimiento

(2S,4R)—N-Boc-4-fluoropyrrolidine-2-carboxylic acid (1.17 g, 5.0 mmol) and NaF (0.63 g, 15 mmol) were taken in a Teflon® reactor and suspended in 10 ml of anhydrous dichloromethane. It was cooled with ice. A solution of 2,2-difluoro-1,3-dimethylimidazolidine (0.817 g, 6.0 mmol) in 2 ml of dichloromethane was slowly added. After 5 minutes stirring, the ice bath was removed and stirring was continued at room temperature for 20 minutes. All the volatiles were removed at reduced pressure and the obtained viscous liquid was mixed with 50 ml of pentane and washed with water (50 ml×2). The organic layer was dried over anhydrous magnesium sulfate and filtered. Removal of solvent at reduced pressure gave 1.06 g of (2S,4R)—N-Boc-4-fluoropyrrolidine-2-carbonyl fluoride (Ie) as a colorless oil. Yield; 90%. 19F NMR (282 MHz, CDCl3) (as a 4:6 mixture of rotamers) δ (ppm) 28.66 (s, 0.4 F, COF), 28.10 (s, 0.6 F, COF), −177.16 (m, 0.4 F, CF), −177.83 (m, 0.6 F, CF): 1H NMR (300 MHz, CDCl3) (as a mixture of rotamers) δ 1.42 (s, 0.6×9H, t-Bu), 1.44 (s, 0.4×9H, t-Bu), 2.0-2.8 (m, 2H), 3.45-4.0 (m, 2H), 4.51 (m, 1H), 5.22 (dm, 1H, J=51.6 Hz): 13C NMR (75 MHz, CDCl3) (as a mixture of two rotamers) δ 90.70 (d, J=179.9 Hz, CF), 91.61 (d, J=179.9 Hz, CF), 153.07 (s, CON), 154.17 (s, CON), 161.90 (d, J=368.4 Hz, COF), 162.11 (d, J=368.4 Hz, COF): IR (Neat, KBr) 1848 (COF) cm−1: High Resolution Mass/ESI-APCI method (solvent; methanol); (M-F+OCH3+Na)+ 270.1114 [calcd 270.1112 for (C11H18FNO4+Na)].

Fuente