Dimethyl Carbonate → HCID 57571718, compound

Sodium methoxide (664 mg, 12 mmol) was added to a solution of the oxazolidinone from preparation 6 (1.17 g, 2.5 mmol) and dimethyl carbonate (1.03 mL, 12 mmol) in dichloromethane (15 mL) and the reaction was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate (50 mL) and water (30 mL). The aqueous layer was neutralised by the addition of 2M HCl (˜6 mL) and then concentrated in vacuo. The residue was triturated with acetonitrile (25 mL) and then filtered. Concentration of the filtrate gave (3S,4S)-1-benzyl-4-(5-chloropyridin-2-yl)pyrrolidine-3-carboxylic acid (123 mg, 16%) as yellow solid (see preparation 8 for spectroscopic data). The ethyl acetate layer was dried (MgSO4) and evaporated. Purification of the residue by column chromatography (silica), eluting with ethyl acetate/pentane 2:8, increasing polarity to 2:3 gave the title compound (371 mg, 45%) as a colourless oil. 1H NMR (CDCl3, 400 MHz) δ2.71 (1H, t), 2.97 (1H, t), 3.05 (2H, m), 3.23 (1H, m), 3.63 (5H, m), 3.82 (1H, q), 7.15-7.35 (6H, m), 7.55 (1H, d), 8.46 (1H, s); LRMS (APCI+) 331 [MH+].

1. concentrationThe reaction mixture was concentrated in vacuo
2. customthe residue was partitioned between ethyl acetate (50 mL) and water (30 mL)
3. additionThe aqueous layer was neutralised by the addition of 2M HCl (˜6 mL)
4. concentrationconcentrated in vacuo
5. customThe residue was triturated with acetonitrile (25 mL)
6. filtrationfiltered
7. customConcentration of the filtrate gave
8. dry with materialThe ethyl acetate layer was dried (MgSO4)
9. customevaporated
10. customPurification of the residue by column chromatography (silica)
11. washeluting with ethyl acetate/pentane 2:8
12. temperatureincreasing polarity to 2:3

ORD record

ord-96fa03f588fe4525ad1603434c711e90

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08138188B2