Methyl iodide → tert-Butyl 4-{(3S)-4-[3-Methoxy-5-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-3-methylpiperazin-1-yl}-4-methylpiperidine-1-carboxylate

To a suspension of sodium hydride (150 mg, 3.75 mmol) in tetrahydrofuran (15 mL) was added a solution of tert-butyl 4-{4-[3-hydroxy-5-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-3-methylpiperazin-1-yl}-4-methylpiperidine-1-carboxylate (92 mg, 0.185 mmol) in tetrahydrofuran (5 mL). The reaction mixture was stirred at room temperature for 1 h before methyl iodide (0.50 mL, 8.05 mmol) was added. The reaction was continuously stirred at room temperature overnight and quenched by addition of 10 mL of water and 10 mL of EtOAc. The organic phase was separated and the aqueous layer was extracted with EtOAc twice (2×15 mL). The combined extracts were washed with brine, dried over Na2SO4, and evaporated under reduced pressure to give the crude product (81 mg, 85%) which was used directly for the next step. LC-MS [M+1]=511.3.

1. additionwas added
2. customquenched by addition of 10 mL of water and 10 mL of EtOAc
3. customThe organic phase was separated
4. extractionthe aqueous layer was extracted with EtOAc twice (2×15 mL)
5. washThe combined extracts were washed with brine
6. dry with materialdried over Na2SO4
7. customevaporated under reduced pressure

ORD record

ord-7948f669c15040a2abd4c4e1f3014372

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09067921B2