Iodoethane → tert-Butyl 4-{(3S)-4-[(1R,2R)-5-Bromo-2-ethoxy-2,3-dihydro-1H-inden-1-yl]-3-methylpiperazin-1-yl}-4-methylpiperidine-1-carboxylate

HRID 2178782Notes

Reaction equation

HRID 2178782 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C@@H:7]([N:11]1[CH2:16][CH2:15][N:14]([C:17]3([CH3:30])[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]3)[CH2:13][C@@H:12]1[CH3:31])[C@H:6]([OH:32])[CH2:5]2.[H-].[Na+].I[CH2:36][CH3:37]>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C@@H:7]([N:11]1[CH2:16][CH2:15][N:14]([C:17]3([CH3:30])[CH2:18][CH2:19][N:20]([C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[CH2:21][CH2:22]3)[CH2:13][C@@H:12]1[CH3:31])[C@H:6]([O:32][CH2:36][CH3:37])[CH2:5]2

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 68741279tert-Butyl 4-{(3S)-4-[(1R,2R)-5-Bromo-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-3-methylpiperazin-1-yl}-4-methylpiperidine-1-carboxylate

Product 1

HCID 68741852tert-Butyl 4-{(3S)-4-[(1R,2R)-5-Bromo-2-ethoxy-2,3-dihydro-1H-inden-1-yl]-3-methylpiperazin-1-yl}-4-methylpiperidine-1-carboxylateYield 82.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 4-{(3S)-4-[(1R,2R)-5-bromo-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-3-methylpiperazin-1-yl}-4-methylpiperidine-1-carboxylate (564 mg, 1.1 mmol) in tetrahydrofuran (20.00 mL) was added sodium hydride (448 mg, 17.75 mmol) at room temperature. After stirring for 10 min, iodoethane (1.42 mL, 17.75 mmol) was added. The reaction mixture was stirred at room temperature overnight and quenched with saturated aqueous ammonium chloride solution (20 mL). The organic layer was separated and the aqueous phase was extracted with ethyl acetate (3×30 mL). The combined extracts were washed with brine, dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure to afford the crude product (488 mg, 82%). LC-MS [M+1]=536.3, 538.8.

Workup

  1. stirringThe reaction mixture was stirred at room temperature overnight
  2. customquenched with saturated aqueous ammonium chloride solution (20 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous phase was extracted with ethyl acetate (3×30 mL)
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-d289a43de0e94eb2b6c754cde9b0ee51
Source dataset
uspto-grants-2015_06
Patent number
US09067921B2

Reaction notes

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