Benzoic Acid → (3R,4S)-[1-benzyloxycarbonyl-4-hydroxypyrrolidin-3-yl]methanol

(3R,4R)-[1-Benzyloxycarbonyl-4-hydroxypyrrolidin-3-yl]methanol (2.50 g), triphenylphosphine (5.74 g), and benzoic acid (2.55 g) were dissolved in tetrahydrofuran (60 mL). While this solution was cooled on a sodium chloride/ice bath, azodicarboxylic acid diethyl ester (40% toluene solution, 9.53 mL) was added dropwise. The mixture was stirred for 1 hour at 0° C. or below and then for additional 2 hours at room temperature and was subsequently concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant=hexane:ethyl acetate=2:1). The eluted pale brown tar-like material was dissolved in ethanol (60 mL). To this solution, potassium carbonate (4.07 g) dissolved in water (30 mL) was added and the mixture was heat-refluxed for 3 hours while being stirred. Subsequently, the reaction mixture was concentrated under reduced pressure, and the resulting residue was dissolved in dichloromethane (200 mL). The dichloromethane solution was washed with a saturated aqueous solution of sodium chloride (2×50 mL), was dried over anhydrous sodium sulfate, and was then concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant=ethyl acetate: methanol=10:1) to give 2.04 g of (3R,4S)-[1-benzyloxycarbonyl-4-hydroxypyrrolidin-3-yl]methanol as a milky white syrup-like product.

1. temperatureWhile this solution was cooled on a sodium chloride/ice bath
2. waitfor additional 2 hours at room temperature
3. concentrationwas subsequently concentrated under reduced pressure
4. customThe resulting residue was purified on a silica gel column (eluant=hexane:ethyl acetate=2:1)
5. dissolutionThe eluted pale brown tar-like material was dissolved in ethanol (60 mL)
6. dissolutionTo this solution, potassium carbonate (4.07 g) dissolved in water (30 mL)
7. additionwas added
8. temperaturethe mixture was heat-refluxed for 3 hours
9. stirringwhile being stirred
10. concentrationSubsequently, the reaction mixture was concentrated under reduced pressure
11. dissolutionthe resulting residue was dissolved in dichloromethane (200 mL)
12. washThe dichloromethane solution was washed with a saturated aqueous solution of sodium chloride (2×50 mL)
13. dry with materialwas dried over anhydrous sodium sulfate
14. concentrationwas then concentrated under reduced pressure
15. customThe resulting residue was purified on a silica gel column (eluant=ethyl acetate: methanol=10:1)

ORD record

ord-7270b6b94e4047eabc34ab8a37456d1c

Source dataset

uspto-grants-2006_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07153851B2