تفاعل #307924

معادلة التفاعل

(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

المردود 90.1%

المذيبات

dichloromethane

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةIt was cooled with ice
2. 2
   أخرىthe ice bath was removed
3. 3
   workup.STIRRINGstirring
4. 4
   workup.WAITwas continued at room temperature for 20 minutes
5. 5
   أخرىAll the volatiles were removed at reduced pressure
6. 6
   workup.ADDITIONthe obtained viscous liquid was mixed with 50 ml of pentane
7. 7
   غسيلwashed with water (50 ml×2)
8. 8
   تجفيفThe organic layer was dried over anhydrous magnesium sulfate
9. 9
   ترشيحfiltered
10. 10
    أخرىRemoval of solvent at reduced pressure

الإجراء التجريبي

(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)].

المصدر