Acetic Acid → HCID 18661335, compound

Temperature

-78 °C

Ethyl (S,S)-2-[1'-(carboxybenzylamino)ethyl]-4-pentenoate (2.19 g, 7.18 mmol) is dissolved in MeOH (50 ml) and the resulting solution cooled to -78° C. O3, from a Welsbach ozonator set at the standard settings, is bubbled through the reaction mixture until starting material can no longer be detected by thin-layer chromatography (2:1 hexane: EtOAc). Dimethyl sulfide (5 ml) is added to the reaction mixture which is allowed to warm to room temperature and is then concentrated by rotary evaporation. The crude aldehyde is dissolved in methanol (25 ml) and tetrahydrofuran (25 ml) and the resulting solution is cooled to 0° C. under a nitrogen atmosphere. Benzyl amine (4.06 ml, 37.15 mmol) followed by acetic acid (4.68 ml, 81.73 mmol) is added to the reaction mixture which is then stirred at 0° C. for 12 min. NaCNBH3 (0.95 g, 14.86 mmol) is added to the reaction mixture which is allowed to warm to room temperature and continuously stirred for a 24 hour period. The reaction mixture is adjusted to pH 9 with 1N NaOH and the resulting mixture is partitioned between EtOAc and water. The layers are separated and the aqueous layer is extracted with EtOAc. The combined organic layers are dried over MgSO4, filtered and then concentrated by rotary evaporation. The crude product is purified by chromatography (1:1 hexane : EtOAc) to give (S,S)-1-benzyl-2-oxo-3-[1'-(carboxybenzylamino)ethyl] pyrrolidine: 1H NMR (300 MHz, CDCl3) δ 1.30 (d, J is 7 Hz, 3H), 1.77 (ddd, J is 16, 12, 9 Hz, 1H), 2.04 (m, 1H), 2.59 (ddd, J is 9, 9, 4 Hz, 1H), 3.04-3.09 (m, 2H), 3.95 (m, 1H), 4.34 (s, 2H), 5.01 (s, 2H), 5.11 (broad s, 1H), 7.10-7.28 (m, 10H),

1. customis bubbled through the reaction mixture
2. additionDimethyl sulfide (5 ml) is added to the reaction mixture which
3. temperatureto warm to room temperature
4. concentrationis then concentrated by rotary evaporation
5. dissolutionThe crude aldehyde is dissolved in methanol (25 ml)
6. temperaturetetrahydrofuran (25 ml) and the resulting solution is cooled to 0° C. under a nitrogen atmosphere
7. additionis added to the reaction mixture which
8. temperatureto warm to room temperature
9. stirringcontinuously stirred for a 24 hour period
10. customthe resulting mixture is partitioned between EtOAc and water
11. customThe layers are separated
12. extractionthe aqueous layer is extracted with EtOAc
13. dry with materialThe combined organic layers are dried over MgSO4
14. filtrationfiltered
15. concentrationconcentrated by rotary evaporation
16. customThe crude product is purified by chromatography (1:1 hexane : EtOAc)

ORD record

ord-20509c24a2554f52921853ff62eed54b

Source dataset

uspto-grants-1998_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05773610