Hydrochloric Acid → (-)-N-Boc-L-4-hydroxyprolinol

Temperature

0 °C

To an ice cold solution of 50.0 g (190 mmol) of 6 in 600 mL of tetrahydrofuran was added 15.0 g (690 mmol) of lithium borohydride in one portion. The mixture was stirred at 0° C. for 1 h followed by 15 h at room temperature. The solution was cooled to 0° C. with stirring and 255 mL of water and 100 mL of 1:1 water:concentrated hydrochloric acid were added carefully. The solution was warmed until an organic phase separated. The organic phase was withdrawn and the aqueous layer was extracted with three 150 mL portions of ethyl acetate. The combined organic layers were washed with 100 mL each of 2 N sodium hydroxide, 2 N hydrochloric acid, and brine. The organic layers were dried over magnesium sulfate and evaporated under reduced pressure to an oil. The oil was kept at 0.05 mm for 24 h and then used without further purification. The yield of 7 was 33.9 g (81%). 1H NMR (CDCl3) δ1.1-2.0 (m), 1.48 (s, 9H), 3.3-4.2 (m), 4.4 (s). 13C NMR (CDCl3) δ28.4, 37.2, 54.9, 55.4, 57.7, 58.4, 63.5, 65.9, 68.6, 80.2, 154.8, 156.5; IR (neat) 3400, 1670, 1420 cm-1.

1. waitfollowed by 15 h at room temperature
2. temperatureThe solution was cooled to 0° C.
3. stirringwith stirring
4. temperatureThe solution was warmed until an organic phase
5. customseparated
6. customThe organic phase was withdrawn
7. extractionthe aqueous layer was extracted with three 150 mL portions of ethyl acetate
8. washThe combined organic layers were washed with 100 mL each of 2 N sodium hydroxide, 2 N hydrochloric acid, and brine
9. dry with materialThe organic layers were dried over magnesium sulfate
10. customevaporated under reduced pressure to an oil
11. waitThe oil was kept at 0.05 mm for 24 h
12. customused without further purification

ORD record

ord-e757a7183cbc4c239034fae6bff61697

Source dataset

uspto-grants-1984_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04424312