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-b7b8d69bb593466bbc5772fb4fb82242

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06881749B2