Triethylamine → (S)-4-Benzyl-3-[(2S,3R)-3-(4-benzyloxy-2-methyl-phenyl)-2-ethoxy-3-hydroxy-propionyl]-oxazolidin-2-one

Temperature

-78 °C

(S)-4-Benzyl-3-ethoxyacetyl-oxazolidin-2-one (12.45 g, 47 mmol) (for the preparation of (S)-4-benzyl-3-ethoxyacetyl-oxazolidin-2-one see: D. Haigh, H. C. Birrell, B. C. C. Cantello, D. S. Eggleston, R. C. Haltiwanger, R. M. Hindley, A. Ramaswamy, N. C. Stevens, Tetrahedron: Asymmetry 1999, 10, 1353-1367) was dissolved in dry dichloromethane (270 ml) under an argon atmosphere and the solution was cooled to −78° C. Triethylamine (7.98 ml, 57 mmol) was added, followed by the slow addition, over approximately 20 min, of di-n-butylboron triflate (1 M solution in dichloromethane, 50 ml, 50 mmol) such that the reaction temperature was kept below −70° C. The mixture was stirred at −78° C. for 50 min, the cooling bath was replaced with an ice bath and the mixture stirred at 0° C. for additional 50 min before being recooled to −78° C. A solution of 4-benzyloxy-2-methyl-benzaldehyde (10.7 g, 47 mmol) in dry dichloromethane (130 ml) was added over ca. 45 min, such that the reaction temperature was maintained below −70° C. The resulting mixture was stirred at −78° C. for 45 min, warmed from −78° C. to 0° C. and stirred at 0° C. for a further 1.5 h. The reaction mixture was poured onto ice water/brine and extracted two times with dichloromethane. The combined extracts were washed with brine and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue purified by column chromatography (silica gel, cyclohexane/AcOEt) to give 22.3 g (45.6 mmol, 96%) of the title compound as colorless oil. According to 1H-NMR spectroscopy, one of the four isomers is strongly predominating. The configuration was tentatively assigned as 2S,3R according to D. Haigh et al., Tetrahedron: Asymmetry 1999, 10, 1353-1367.

1. customwas kept below −70° C
2. customthe cooling bath was replaced with an ice bath
3. stirringthe mixture stirred at 0° C. for additional 50 min
4. custombefore being recooled to −78° C
5. temperaturewas maintained below −70° C
6. stirringThe resulting mixture was stirred at −78° C. for 45 min
7. temperaturewarmed from −78° C. to 0° C.
8. stirringstirred at 0° C. for a further 1.5 h
9. additionThe reaction mixture was poured onto ice water/brine
10. extractionextracted two times with dichloromethane
11. washThe combined extracts were washed with brine
12. dry with materialdried over sodium sulfate
13. customThe solvent was removed under reduced pressure
14. customthe residue purified by column chromatography (silica gel, cyclohexane/AcOEt)

ORD record

ord-635f662eeff045ef94a6068b0d50934a

Source dataset

uspto-grants-2005_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06969725B2