Water → HCID 68742358, compound

HRID 2244918Notes

Reaction equation

HRID 2244918 reaction equation
[H-].[Na+].[OH:3][CH:4]1[CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:10]=2)[CH:5]1[N:17]1[CH2:22][CH2:21][N:20]([C:23]2([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]2)[CH2:19][C@@H:18]1[CH3:37].I[CH2:39][CH3:40].O>CN(C=O)C>[CH2:39]([O:3][CH:4]1[CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:13]([F:16])([F:14])[F:15])[CH:10]=2)[CH:5]1[N:17]1[CH2:22][CH2:21][N:20]([C:23]2([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]2)[CH2:19][C@@H:18]1[CH3:37])[CH3:40]

Participants

6

Reactant 4

HCID 962WaterHCID 6340IodoethaneHCID 24758Sodium hydrideHCID 68744726HCID 68744726, compound

Product 1

HCID 68742358HCID 68742358, compoundYield 91.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (5.225 g, 0.1306 mol) was mixed with dry DMF (150 mL) at 0° C. A solution of t-butyl 4-{(3S)-4-[2-hydroxy-5-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-3-methylpiperazin-1-yl}-4-methylpiperidine-1-carboxylate (50.0 g, 0.1005 mol) in DMF (100 mL) was added dropwise at 0° C over 20 min. After the addition, the mixture was stirred for another 20 min before iodoethane (12.06 mL, 0.1507 mol) was added at one portion. After being stirred for 1 h, the reaction content was carefully poured into 500 mL icy water. The mixture was extracted with methylene chloride (500 mL×3). The combined organic layer was washed with brine, and dried over magnesium sulfate. After the removal of the solvent, the residue was dissolved in methylene chloride, and passed through a silica plug with ethyl acetate/hexane/triethylamine 50:50:1 (the plug was presaturated with the same solvent system). After removal of the solvent, 48.4 g (91.6%) of product was obtained as a sticky solid, MS (EI) 526.2 (M+1).

Workup

  1. additionAfter the addition
  2. additionwas added at one portion
  3. extractionThe mixture was extracted with methylene chloride (500 mL×3)
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. customAfter the removal of the solvent
  7. dissolutionthe residue was dissolved in methylene chloride
  8. customAfter removal of the solvent

Sources & evidence

ORD record
ord-81978ea6709d48feae4942c86e2745cd
Source dataset
uspto-grants-2010_03
Patent number
US07678798B2

Reaction notes

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