Acetyl chloride → HCID 10590693, compound

Acetyl chloride (1.50 ml, 21.10 mmol) was added dropwise to MeOH (7.5 mL) at 0° C. After 15 min of stirring a solution of 3-((2R,5S)-1-benzyl-5-(tert-butoxycarbonyl)pyrrolidin-2-yl)propanoic acid (200 mg, 0.600 mmol) in MeOH (7.5 mL) was slowly added to the reaction. The reaction mixture was then heated at reflux overnight. The reaction was concentrated. The residue was partitioned between EtOAc and 10% Na2CO3. The organic phase was separated, washed with saturated aqueous NaCl solution, dried over MgSO4, filtered and concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) to give the product (2S,5R)-methyl 1-benzyl-5-(3-methoxy-3-oxopropyl)pyrrolidine-2-carboxylate (126 mg, 0.413 mmol, 68.8% yield) as colorless syrup. 1HNMR (400 MHz, CDCl3) δ ppm 7.35-7.17 (5 H, m), 3.95 (1 H, d, J=13.7 Hz), 3.71-3.61 (4 H, m), 3.47 (3 H, s), 3.37-3.26 (1 H, m), 2.86-2.73 (1 H, m), 2.53-2.41 (1 H, m), 2.38-2.25 (1 H, m), 2.08-1.79 (4 H, m), 1.79-1.66 (1 H, m), 1.66-1.53 (1 H, m).

1. additionwas slowly added to the reaction
2. temperatureThe reaction mixture was then heated
3. temperatureat reflux overnight
4. concentrationThe reaction was concentrated
5. customThe residue was partitioned between EtOAc and 10% Na2CO3
6. customThe organic phase was separated
7. washwashed with saturated aqueous NaCl solution
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customThe resulting residue was purified

ORD record

ord-d53ae51ab8dd4441bf2467261c56ef16

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08815909B2