Aluminium lithium hydride → HCID 58118714, compound

To a stirred solution of methyl[(8R)-8-(3,5-difluorophenyl)-8-methyl-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]acetate from Step A (998 mg, 2.83 mmol) in THF (14 mL) cooled to 0° C. via an ice/water bath was added LiAlH4 (1 M in THF, 4.20 mL, 4.20 mmol). After 40 min, the reaction was quenched with water (40 mL), and the resulting mixture was filtered through Celite, washing with saturated NaHCO3 solution (50 mL) and EtOAc (80 mL). The filtrate was separated and the aqueous layer was extracted an additional time with EtOAc (80 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of EtOAc:Hexanes—0:100 to 100:0. The clean fractions were concentrated in vacuo to yield the title compound. MS: m/z=325 (M+1).

1. customthe reaction was quenched with water (40 mL)
2. filtrationthe resulting mixture was filtered through Celite
3. washwashing with saturated NaHCO3 solution (50 mL) and EtOAc (80 mL)
4. customThe filtrate was separated
5. extractionthe aqueous layer was extracted an additional time with EtOAc (80 mL)
6. dry with materialThe combined organic layers were dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude product was purified by silica gel chromatography
10. washeluting with a gradient of EtOAc
11. concentrationThe clean fractions were concentrated in vacuo

ORD record

ord-9801de2562e3402a87ab080f62931f8f

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08765759B2