tert-Butyl 3-hydroxy-3-Methylpyrrolidine-1-carboxylate Chemical Properties

Boiling point:

277.2±33.0 °C(Predicted)

Density 

1.103±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

pka

14.80±0.20(Predicted)

Appearance

White to light brown Solid

tert-Butyl 3-hydroxy-3-Methylpyrrolidine-1-carboxylate Usage And Synthesis

Synthesis

At -10 °C, 4 L of anhydrous tetrahydrofuran (THF) was added to a 30 L reaction kettle. After initiating stirring, zinc chloride (118 g, 0.86 mol) and lithium chloride (402 g, 9.5 mol) were added sequentially to the reactor. After half an hour, an ether solution (6.4 L, 19.2 mol) of methylmagnesium bromide (3 mol/L) was added slowly and dropwise to the reaction mixture. Stirring was continued for half an hour. Subsequently, a THF solution of 1-tert-butoxycarbonyl-3-pyrrolidone (1600 g, 8.6 mol) was added slowly dropwise. The progress of the reaction was monitored by high performance liquid chromatography (HPLC) and after confirming the completion of the reaction, saturated ammonium chloride (NH4Cl) solution was added slowly and dropwise to quench the reaction. The reaction mixture was extracted with ethyl acetate and the organic phase was washed with saturated aqueous sodium chloride (NaCl) solution and dried with anhydrous sodium sulfate. Finally, the solvent was removed by evaporation to afford the target product tert-butyl 3-hydroxy-3-methylpyrrolidine-1-carboxylate as a light yellow solid (1450 g) in 83.8% yield.

References

[1] Patent: US2013/252938, 2013, A1. Location in patent: Paragraph 0514
[2] Patent: US2014/45896, 2014, A1. Location in patent: Paragraph 0134; 0135; 0199; 0200
[3] Patent: EP2703398, 2014, A1. Location in patent: Paragraph 0119; 0120
[4] Patent: EP2703398, 2014, A1. Location in patent: Paragraph 0173; 0174
[5] Journal of the American Chemical Society, 2015, vol. 137, # 35, p. 11270 - 11273

tert-Butyl 3-hydroxy-3-Methylpyrrolidine-1-carboxylate(412278-02-5)Related Product Information

• 1-Piperidinecarboxylic acid, 3-hydroxy-4,4-diMethoxy-, 1,1-diMethylethyl ester
• 4-(4-Aminophenyl)piperazine-1-carboxylic acid tert-butyl ester