Benzyl chloroformate → (3R,4R)-(1-benzyloxycarbonyl-4-hydroxypyrrolidin-3-yl)methanol

Sodium hydroxide (2.70 g) was dissolved in water (25 mL) and dioxane (15 mL) was added. To this solution, (3R,4R)-(4-hydroxypyrrolidin-3-yl)methanol (1.00 g) was dissolved. While the solution was cooled on an ice bath, carbobenzoxy chloride (0.97 mL) was added dropwise. The mixture was stirred at 5° C. or below for 1 hour, followed by dropwise addition of carbobenzoxy chloride (0.97 mL). The mixture was further stirred at 5° C. or below for additional 1 hour and carbobenzoxy chloride (0.97 mL) was subsequently added dropwise. This was followed by stirring for 1 hour at 5° C. or below and another 1 hour at room temperature. Subsequently, the reaction mixture was extracted with dichloromethane (2×100 mL). The dichloromethane extracts were combined, and the combined dichloromethane layer was dried over anhydrous sodium sulfate and was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant=hexane:ethyl acetate=1:1 shifted to ethyl acetate: methanol=20:1) to give 1.18 g of (3R,4R)-[1-benzyloxycarbonyl-4-hydroxypyrrolidin-3-yl]methanol as a milky white tar-like product.

1. temperatureWhile the solution was cooled on an ice bath
2. stirringThe mixture was further stirred at 5° C. or below for additional 1 hour
3. stirringby stirring for 1 hour at 5° C. or below and another 1 hour at room temperature
4. extractionSubsequently, the reaction mixture was extracted with dichloromethane (2×100 mL)
5. dry with materialthe combined dichloromethane layer was dried over anhydrous sodium sulfate
6. concentrationwas concentrated under reduced pressure
7. customThe resulting residue was purified on a silica gel column (eluant=hexane:ethyl acetate=1:1 shifted to ethyl acetate: methanol=20:1)

ORD record

ord-6a2cc5fadca84b6b90f95c0f226519e9

Source dataset

uspto-grants-2006_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07153851B2