Reaction #527256

Reaction equation

N-methyl proline methyl ester

HCl

acetone oxime

butane

n-BuLi

→

crude product

1-(1-methyl-2(S)-pyrrolidinyl)-1,3-butanedione-3-oxime

Solvents

THF

THF

hexane

Conditions

Workup

1. 1
   OtherThe layers were separated
2. 2
   Washthe aqueous layer was washed with ether (1000 mL)
3. 3
   Extractionextracted with methylene chloride (4×800 mL)
4. 4
   DryingThe combined methylene chloride layers were dried (MgSO4)
5. 5
   Concentrationconcentrated

Procedure

To n-BuLi (Aldrich, 2.5M in hexane, 61 4 mL, 1.53 mol, 4.4 eq.), diluted to 1.6M with hexane (342 mL), under argon at 0° C. was added a solution of acetone oxime (Aldrich, 56.15 g, 768 mmol, 2.2 eq.; recrystallized 1x hexanes) in THF (500 mL) dropwise over a 90 minute period (butane evolved!). After an additional 2 hours at 0° C. a solution of N-methyl proline methyl ester (50.0 g, 349 mmoL, 1.0 eq., the product of step 1b above) in THF (75 mL) was added over a 90 minute period. After stirring an additional 20 hours at 0° C. the reaction mixture was slowly cannulated into a vigorously stirred solution of 10% aq. HCl (1700 mL, cooled to 0° C.) over a 40 minute period. The layers were separated and the aqueous layer was washed with ether (1000 mL), then adjusted to pH ~9-10 with NaHCO3 /Na2CO3 (solid) and extracted with methylene chloride (4×800 mL). The combined methylene chloride layers were dried (MgSO4) and concentrated to afford the crude product as a pale yellow oil, (53.62 g), along with 10-20% of the N-oxide byproduct (by NMR integration). MS (Cl, DCl/N H3) m/e 185 (M+H)+. 1NMR (CDCl3) δ: 1.57-1.91 (br.m., 4H); 2.02 (s, 3H); 2.42-2.52 (m, 1H); 2.53 (s, 3H); 2.75 (dd, 1H); 2.80 (d, 2H); 3.15 (m, 1H).

Source