HCID 67296619, compound → HCID 67296569, compound

To a mixture of (S)-1-methyl-5-((tetrahydro-2H-pyran-2-yloxy)methyl)-pyrrolidin-2-one (0.6 g, 2.82 mmol) in 20 mL of THF was added Ti(Oi-Pr)4 (2.56 mL, 8.45 mmol, d=0.937 g/L, Aldrich) via a syringe under nitrogen at rt. After stirring at rt for 30 min, EtMgBr (5.63 mL, 16.9 mmol, 3M ether solution, Aldrich) was added via a syringe pump over 3 hrs. The reaction was continued to stir at rt overnight, and then quenched with a mixture of 20 mL of water and 30 mL of ethyl acetate. After stirring for 20 min, the mixture was filtered through a celite pad. The filtrate was extracted with ethyl acetate (30 mL×3). The combined organic phases were dried over Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (50:1(v/v) CH2Cl2/CH3OH) to afford (5S)-4-methyl-5-((tetrahydro-2H-pyran-2-yloxy)methyl)-4-azaspiro[2.4]heptane as pale yellow oil (64 mg, 10%).

1. stirringto stir at rt overnight
2. customquenched with a mixture of 20 mL of water and 30 mL of ethyl acetate
3. stirringAfter stirring for 20 min
4. filtrationthe mixture was filtered through a celite pad
5. extractionThe filtrate was extracted with ethyl acetate (30 mL×3)
6. dry with materialThe combined organic phases were dried over Na2SO4
7. concentrationconcentrated in vacuo
8. customThe residue was purified by a silica gel column chromatography (50:1(v/v) CH2Cl2/CH3OH)

ORD record

ord-c991656b3b2140369e8672f14bdb327e

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426585B2