반응 #158404

반응 방정식

4-formylbenzonitrile

azetidine-3-carboxylic acid

acetic acid

Sodium triacetoxyborohydride

→

1-(4-cyanobenzyl)azetidine-3-carboxylic acid

수율 75.0%

용매

dichloromethane

methanol

반응 조건

후처리

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued at room temperature for 18 hr
3. 3
   기타The volatiles were removed under reduced pressure
4. 4
   기타the residue was partitioned between water (50 mL) and diethyl ether (50 mL)
5. 5
   세척The aqueous phase was washed with diethyl ether (50 mL)
6. 6
   농축was then concentrated to dryness
7. 7
   workup.DISSOLUTIONThe residue was dissolved in water (20 mL)
8. 8
   기타column [Preparation of HP-20 Gel
9. 9
   기타˜400 ml of dry
10. 10
    workup.WAITunused MCI CHP-20 Gel (75-150 micron) was swelled in methanol for 24 hrs
11. 11
    여과The gel was filtered
12. 12
    세척rinsed with 1 liter of methanol
13. 13
    세척Immediately before use, the desired amount of gel was rinsed thoroughly with 20 volumes of water]
14. 14
    세척The column was eluted with 240 mL of water and 400 mL of methanol
15. 15
    workup.ADDITIONThe product containing fractions
16. 16
    농축were concentrated

실험 절차

A mixture of 4-formylbenzonitrile (2.88 g, 22.0 mmol), azetidine-3-carboxylic acid (2.02 g, 20 mmol), and acetic acid (1.15 mL, 20.0 mmol) in dichloromethane (20 mL) and methanol (80 mL) was stirred at room temperature for 1 h. Sodium triacetoxyborohydride (6.78 g, 32.0 mmol) was added and stirring was continued at room temperature for 18 hr. The volatiles were removed under reduced pressure, and the residue was partitioned between water (50 mL) and diethyl ether (50 mL). The aqueous phase was washed with diethyl ether (50 mL) and was then concentrated to dryness. The residue was dissolved in water (20 mL) and loaded onto a 2.5×20 cm HP-20 column [Preparation of HP-20 Gel: ˜400 ml of dry, unused MCI CHP-20 Gel (75-150 micron) was swelled in methanol for 24 hrs. The gel was filtered and rinsed with 1 liter of methanol. It was then transferred to a bottle for storage under methanol. Immediately before use, the desired amount of gel was rinsed thoroughly with 20 volumes of water]. The column was eluted with 240 mL of water and 400 mL of methanol. The product containing fractions were concentrated and co-evaporated from ethanol and ethyl acetate/heptane to afford 1-(4-cyanobenzyl)azetidine-3-carboxylic acid (3.25 g, 15.0 mmol, 75% yield) as a white solid. MS: (M+H)=217.18. 1H NMR (400 MHz, MeOD) δ ppm 3.39 (m, 1H), 4.08 (m, 4H), 4.32 (s, 2H), 7.63 (d, J=8.3 Hz, 2H), and 7.82 (d, J=8.3 Hz, 2H).

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