Potassium Iodide → methyl 4-({2-[(5R)-5-(hydroxymethyl)-2-oxo pyrrolidin-1-yl]ethyl}thio)butanoate

温度

50 °C

To a solution of (5R)-5-(1-ethoxyethoxymethyl)pyrrolidin-2-one (3.31 g, 17.7 mmol) in 50 mL of anhydrous dimethylformamide at 0° C. under an argon atmosphere was added potassium iodide (3.22 g, 19.4 mmol) and sodium hydride (95%, 0.44 g, 17.7 mmol). The cooling bath was removed and the reaction was stirred for 30 minutes. A solution of methyl 4-[(2-chloroethyl)thio]butanoate (3.46 g, 17.7 mmol) in 5 mL anhydrous dimethylformamide was added and the reaction solution was warmed to 50° C. and stirred for 40 hours. The volatiles were removed via simple distillation under vacuum. Ethyl acetate (150 mL) and aqueous ammonium chloride solution (50 mL) were then added to the crude residue. Upon separation between the two phases, the ethyl acetate solution was dried (anhydrous. Na2SO4) and evaporated under reduced pressure. To a solution of the protected ester (17.7 mmol) in 70 mL of anhydrous methanol at room temperature under an argon atmosphere was added p-toluenesulfonic acid monohydrate (0.34 g, 1.8 mmol). After stirring for 5 hours, aqueous sodium bicarbonate solution (50 mL) was added and the reaction mixture was evaporated under reduced pressure. Ethanol (50 mL) was added and the solution was again evaporated. The resultant material was purified via column chromatography to yield methyl 4-({2-[(5R)-5-(hydroxymethyl)-2-oxo pyrrolidin-1-yl]ethyl}thio)butanoate as a tan oil (0.17 g, mass spec. M+=275).

1. customThe cooling bath was removed
2. stirringstirred for 40 hours
3. customThe volatiles were removed via simple distillation under vacuum
4. additionEthyl acetate (150 mL) and aqueous ammonium chloride solution (50 mL) were then added to the crude residue
5. customUpon separation between the two phases
6. dry with materialthe ethyl acetate solution was dried (anhydrous. Na2SO4)
7. customevaporated under reduced pressure
8. stirringAfter stirring for 5 hours
9. customthe reaction mixture was evaporated under reduced pressure
10. additionEthanol (50 mL) was added
11. customthe solution was again evaporated
12. customThe resultant material was purified via column chromatography

ORDレコード

ord-918278a3e92a46f7a48ad50ed9490c52

出典データセット

uspto-grants-2005_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06849657B2