反応 #307924

反応方程式

(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

収率 90.1%

溶媒

dichloromethane

dichloromethane

反応条件

後処理

1. 1
   温度It was cooled with ice
2. 2
   その他the ice bath was removed
3. 3
   workup.STIRRINGstirring
4. 4
   workup.WAITwas continued at room temperature for 20 minutes
5. 5
   その他All the volatiles were removed at reduced pressure
6. 6
   workup.ADDITIONthe obtained viscous liquid was mixed with 50 ml of pentane
7. 7
   洗浄washed with water (50 ml×2)
8. 8
   乾燥The organic layer was dried over anhydrous magnesium sulfate
9. 9
   ろ過filtered
10. 10
    その他Removal of solvent at reduced pressure

実験手順

(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)].

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