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

HRID 2244935Notes

Reaction equation

HRID 2244935 reaction equation
[H-].[Na+].[OH:3][CH:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([F:16])([F:15])[F:14])[CH:11]=2)[CH:6]([N:17]2[CH2:22][CH2:21][N:20]([C:23]3([CH3:36])[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]3)[CH2:19][CH:18]2[CH3:37])[CH2:5]1.[CH3:38]I>O1CCCC1>[CH3:38][O:3][CH:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([F:16])([F:14])[F:15])[CH:11]=2)[CH:6]([N:17]2[CH2:22][CH2:21][N:20]([C:23]3([CH3:36])[CH2:24][CH2:25][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:27][CH2:28]3)[CH2:19][C@@H:18]2[CH3:37])[CH2:5]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 68741680tert-butyl 4-{4-[3-hydroxy-5-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-3-methylpiperazin-1-yl}-4-methylpiperidine-1-carboxylate

Product 1

HCID 86601777tert-Butyl 4-{(3S)-4-[3-Methoxy-5-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-3-methylpiperazin-1-yl}-4-methylpiperidine-1-carboxylateYield 85.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-ea806368d5db4bbd88ec6f66ddf80034
Source dataset
uspto-grants-2010_03
Patent number
US07678798B2

Reaction notes

Loading…