HCID 178418255, compound → HCID 60036805, compound

Temperature

-78 °C

The silylated imine from the previous step, e.g. (2R)-3-methyl-N—[(E)-2-pyridinylmethylidene]-1-[(trimethylsilyl)oxy]-2-butanamine was dissolved in dry THF (500 ml) and the solution was cooled down to −78° C. A 1 M solution of phenylmagnesiumbromide in THF (200 ml, 200 mmol, 2 eq) was added dropwise while the mixture was stirred by a magnetic bar. The mixture was further stirred 2 hours at −78° C. The temperature was then slowly increased up to room temperature overnight. A sample of the reaction mixture was quenched with aqueous NaHCO3 and analysed by LC-MS to detect the O-silylated products. After one night, the mixture was quenched with HCl 1M (250 ml) and the mixture was stirred at room temperature until the desilylation was complete (after 1 h, LC/MS analysis). The aqueous phase was further acidified with the addition of 5M HCl solution (20 ml). The aqueous phase was washed with 300 ml cyclohexane/Et2O (2:1), then made basic with 60 ml NaOH 5M at 0° C., and the organic products were extracted with Et2O, dried (MgSO4) and concentrated to give the desired product (XX*), e.g. (2R)-3-methyl-2-{[(R)-phenyl(2-pyridinyl)methyl]amino}-1-butanol as a yellowish oil (22.9 g, 85% yield, d.e.=99%, determined by 1H NMR).

1. temperatureThe temperature was then slowly increased up to room temperature overnight
2. customA sample of the reaction mixture was quenched with aqueous NaHCO3 and analysed by LC-MS
3. waitAfter one night
4. customthe mixture was quenched with HCl 1M (250 ml)
5. stirringthe mixture was stirred at room temperature until the desilylation
6. custom(after 1 h, LC/MS analysis)
7. additionThe aqueous phase was further acidified with the addition of 5M HCl solution (20 ml)
8. washThe aqueous phase was washed with 300 ml cyclohexane/Et2O (2:1)
9. custommade basic with 60 ml NaOH 5M at 0° C.
10. extractionthe organic products were extracted with Et2O
11. dry with materialdried (MgSO4)
12. concentrationconcentrated

ORD record

ord-2b74db576fb8459090ca6a1f4844498a

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08415480B2