Tetrahydrofuran → 4-Benzyloxy-2-((S)-2-hydroxy-propylamino)-benzaldehyde

To a solution of the product of Step B (19.3 g, 68.3 mmol) in a mixture of anhydrous cyclohexane and THF (200 mL, 40 mL) at 0° C. under nitrogen was added diisobutylammonium hydride (1 M solution in hexane, 239 mL, 239 mmol) over 30 min. This mixture was stirred 18 h at ambient temperature, additional diisobutylammonium hydride (40 mL, 40 mmol) was added, and the mixture was stirred an additional 24 h. The reaction mixture was cooled on an ice bath and the reaction was quenched by the addition of MeOH (exothermic) and 2 N HCl to maintain a pH of 1. The mixture was extracted with EtOAc (3×300 mL) and the extracts were dried and concentrated to a brown oil (18.5 g). The crude oil was triturated with EtOAc/hexane, and filtered to give an oil (16.1 g, 83% crude yield). A small portion of this material was purified by chromatography (silica, 20% to 50% EtOAc/hexane) to afford a solid; mp 68-69° C.

1. stirringthe mixture was stirred an additional 24 h
2. temperatureThe reaction mixture was cooled on an ice bath
3. customthe reaction was quenched by the addition of MeOH (exothermic) and 2 N HCl
4. temperatureto maintain a pH of 1
5. extractionThe mixture was extracted with EtOAc (3×300 mL)
6. customthe extracts were dried
7. concentrationconcentrated to a brown oil (18.5 g)
8. customThe crude oil was triturated with EtOAc/hexane
9. filtrationfiltered
10. customto give an oil (16.1 g, 83% crude yield)
11. customA small portion of this material was purified by chromatography (silica, 20% to 50% EtOAc/hexane)
12. customto afford a solid

ORD record

ord-202fd374d0be422ea5750f3b47702d27

Source dataset

uspto-grants-2004_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06696476B2