4-Hydroxy-1,3-pyrrolidinedicarboxylic acid 1-(1,1-dimethylethyl) 3-ethyl ester synthesis

Yield:146256-99-7 98.9%

Reaction Conditions:

with sodium tetrahydroborate in methanol at 10; for 0.833333 h;

Steps:

2.2 4.2.2. tert-Butyl 3-ethyl 4-hydroxypyrrolidine-1,3-dicarboxylate 2a

4.2.2
tert-Butyl 3-ethyl 4-hydroxypyrrolidine-1,3-dicarboxylate 2a
To a suspension of NaBH₄ (2.74 g, 72.3 mmol) in anhydrous methanol (290 mL) was added 1a (37.19 g, 144.6 mmol) at below 10 °C.
The reaction mixture was stirred at the same temperature for 50 min, and then 20% aqueous acetic acid was added dropwise to adjust pH 7.0 at 0 °C, and then concentrated under reduced pressure.
The residue was dissolved with ethyl acetate (400 mL), and washed with water (50 mL * 3), brine (40 mL * 2), dried over anhydrous sodium sulfate, and evaporated under vacuo to afford the title compound 2a (37.11 g, 98.9%) as a pale yellow oil. ¹H NMR (400 MHz, CDCl₃) δ (ppm): 4.53-4.42 (m, 1H), 4.16-4.08 (m, 2H), 3.36-3.60 (m, 2H), 3.43 (brs, 1H), 3.28-3.25 (brs, 2H), 3.01-2.97 (brs, 1H), 1.42 (s, 9H), 1.28-1.21 (m, 3H). MS-ESI (m/z): 282.75 (M + Na)⁺.

References:

Zhang, Tingting;Shen, Weiyi;Liu, Mingliang;Zhang, Rui;Wang, Minghua;Li, Linhu;Wang, Bin;Guo, Huiyuan;Lu, Yu [European Journal of Medicinal Chemistry,2015,vol. 104,p. 73 - 85]