Water → HCID 68670481, compound

H2O (0.0953 g, 0.71 mmol, 1.1 eq) was added to a stirred solution of (R)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (0.1615 g, 0.64 mmol, 1 eq) in 5 ml anhydrous CH2Cl2 at 0° C. under Ar. After 30 min EDCI.HCl (0.135 g, 0.71 mmol, 1.1 eq) was added. After 1 h 1,1-Dimethylhydrazine (0.058 ml, 0.046 g, 0.77 mmol, 1.2 eq) and DIPEA (0.33 ml, 0.25 g, 1.92 mmol, 3 eq) were added sequentially. The reaction was stirred at 0° C. to room temperature overnight. The solvent was removed in vacuo and the residue partitioned between EtOAc/water. The layers were separated. The aqueous layer was saturated with NaCl and extracted with EtOAc (×2). The combined EtOAc fractions were dried over Na2SO4. The inorganics were filtered off, and the solvent removed in vacuo. Purification via flash chromatography yielded 0.1489 g, 0.51 mmol, 79% yield) of (R)-tert-butyl 2-(2,2-dimethylhydrazinecarbonyl)pyrrolidine-1-carboxylate with some impurity. TFA (0.5 ml, 0.74 g, 6.49 mmol) was added to a stirred solution of (R)-tert-butyl 2-(2,2-dimethylhydrazinecarbonyl)pyrrolidine-1-carboxylate (0.045 g, 0.155 mmol, 1 eq) in anhydrous CH2Cl2 under Ar. After 1 h the solvent was removed in vacuo to generate (R)—N′,N′-dimethylpyrrolidine-2-carbohydrazide.

1. customThe solvent was removed in vacuo
2. customthe residue partitioned between EtOAc/water
3. customThe layers were separated
4. extractionextracted with EtOAc (×2)
5. dry with materialThe combined EtOAc fractions were dried over Na2SO4
6. filtrationThe inorganics were filtered off
7. customthe solvent removed in vacuo
8. customPurification via flash chromatography

ORD record

ord-88ea348409b54647a3de68d92ad31648

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08299267B2