Benzyl acetate → Benzyl(4r,5s)-4-(tert-butoxycarbonylamino)-5-methyl-3-oxoheptanoate

To a solution of Boc-D-alloIle-OH (15.26 g, 65.9 mmol) in dry THF (200 ml) at 0° C. under argon, was added CDI (16.04 g, 98.96 mmol). After 15 min, the mixture was allowed to warm to room temperature, and stirred over a period of 16 h. The resulting solution was cooled to −78° C., and added via cannula to a well stirred solution of benzyl lithium enolate cooled at −78° C. (625 ml, 0.37 M), [prepared by adding dropwise a solution of benzyl acetate (33.34 ml), in THF (165 ml) to a solution of lithium diisopropylamide (0.36M) in THF/hex 3:1 (642 ml) at −78° C.]. The temperature should be kept <−75° C. The reaction mixture was stirred at −78° C. for 60 min. Then, it was allowed to come to −10° C. (30 min), recooled to −78° C. and quenched with saturated aq. ammonium chloride (200 ml), then extracted with DCM (3×500 ml) at room temperature. The combined extracts were washed successively with aq sat. NaHCO3 (500 ml) and brine (200 ml). Drying (Na2SO4) followed by removal of solvent gave an oil, which was coated on silica C18 and loaded to the top of a LC-RPC18 [Lichroprep RPC-18 (40-60 microns) column. Elution using a gradient ACN-H2O (60 to 100% ACN)] yielded the product C4 as a colourless oil (16.7 g, 70%). [α]20D −20.0 (c 1, CHCl3), TLC: Rf=0.32 (Merck, RP-C18, ACN-H2O 7:3).

1. temperatureThe resulting solution was cooled to −78° C.
2. additionadded via cannula to a well
3. temperaturecooled at −78° C. (625 ml, 0.37 M)
4. custom[prepared
5. customat −78° C.
6. customshould be kept <−75° C
7. stirringThe reaction mixture was stirred at −78° C. for 60 min
8. customto come to −10° C.
9. custom(30 min)
10. customrecooled to −78° C.
11. customquenched with saturated aq. ammonium chloride (200 ml)
12. extractionextracted with DCM (3×500 ml) at room temperature
13. washThe combined extracts were washed successively with aq sat. NaHCO3 (500 ml) and brine (200 ml)
14. dry with materialDrying (Na2SO4)
15. customfollowed by removal of solvent
16. customgave an oil, which
17. washElution

ORD record

ord-3a9e0fe171b24dadb9203375c05e37b7

Source dataset

uspto-grants-2010_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07678765B2