9-Fluorenylmethyl chloroformate → (2S,3S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)-3-hydroxypyrrolidine-2-carboxylic acid

To a stirred and cooled suspension of trans-3-hydroxy-(L)-proline (2.00 g, 15.3 mmol, 1.00 eq.) in 1,4-dioxane (110 mL) and aq. NaHCO3 (5% w/v, 55 mL) was added slowly a solution of Fmoc-Cl (4.02 g, 15.56 mmol, 1.02 eq.) in dioxane (50 mL). The reaction mixture was kept at 4° C. for 4 h, allowed to warm to room temperature, and stirred for another 6 h to afford a clear, colorless solution. Most of the dioxane was evaporated in vacuo (45° C. bath temperature), and the resultant solution was extracted with diethyl ether (2×100 mL) to remove excess Fmoc-Cl. The aqueous layer was acidified to pH 2-3 with 1 M HCl to afford a cloudy solution, which was extracted with EtOAc (4×100 mL). The combined organic layers were dried (MgSO4), filtered, evaporated in vacuo and co-evaporated twice with CH2Cl2. Drying under vacuum afforded the product as an off-white, microcrystalline solid (3.10 g, expected 5.39 g, yield 58%). Spectroscopic data were in agreement with the literature (Taylor, Hardre et al. 2005).

1. temperaturecooled
2. stirringstirred for another 6 h
3. customto afford a clear, colorless solution
4. customMost of the dioxane was evaporated in vacuo (45° C. bath temperature)
5. extractionthe resultant solution was extracted with diethyl ether (2×100 mL)
6. customto remove excess Fmoc-Cl
7. customto afford a cloudy solution, which
8. extractionwas extracted with EtOAc (4×100 mL)
9. dry with materialThe combined organic layers were dried (MgSO4)
10. filtrationfiltered
11. customevaporated in vacuo
12. customDrying under vacuum
13. customafforded the product as an off-white, microcrystalline solid (3.10 g

ORD record

ord-906177e0d781457db424edcd1bd8cdfb

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09228224B2