Water → tert-butyl (1S,2R)-1-{benzyl[(1R)-1-phenylethyl]amino}-5-methylindane-2-carboxylate

HRID 64423

Reaction equation

HRID 64423 reaction equation
[CH2:1]([NH:8][C@@H:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.Br[CH2:23][C:24]1[CH:29]=[C:28]([CH3:30])[CH:27]=[CH:26][C:25]=1/[CH:31]=[CH:32]/[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34].O>C1COCC1>[CH2:1]([N:8]([C@@H:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:10])[C@@H:31]1[C:25]2[C:24](=[CH:29][C:28]([CH3:30])=[CH:27][CH:26]=2)[CH2:23][C@H:32]1[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 1268086(+)-BenzylphenethylamineHCID 86713431tert-butyl (2E)-3-[2-(bromomethyl)-4-methylphenyl]acrylateHCID 178418339Butyllithium

Product 1

HCID 86713432tert-butyl (1S,2R)-1-{benzyl[(1R)-1-phenylethyl]amino}-5-methylindane-2-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1.5 ml of (1R)—N-benzyl-1-phenylethanamine in 40 ml of THF was added 4.35 ml of n-butyllithium (1.62 M hexane solution) at −78° C., followed by stirring for 30 minutes. At the same temperature, a solution of 1.00 g of tert-butyl (2E)-3-[2-(bromomethyl)-4-methylphenyl]acrylate in 5 ml of THF was added thereto, followed by stirring for 1.5 hours. To the reaction mixture was added water, followed by warming to room temperature. The solvent was evaporated under reduced pressure and ethyl acetate was then added thereto to carry out a layer separation operation. The organic layer was washed with a 1 M aqueous citric acid solution, water, and saturated brine in this order, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 1.17 g of tert-butyl (1S,2R)-1-{benzyl[(1R)-1-phenylethyl]amino}-5-methylindane-2-carboxylate. Further, the present Preparation Example is in accordance with the method described in a reference (Synlett, 1999, No. 12, 1919-1920 by D. A. Price).

Workup

  1. stirringby stirring for 1.5 hours
  2. customThe solvent was evaporated under reduced pressure and ethyl acetate
  3. additionwas then added
  4. customa layer separation operation
  5. washThe organic layer was washed with a 1 M aqueous citric acid solution, water, and saturated brine in this order
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-61522ff0bd174fc3a33c5180e19684c0
Source dataset
uspto-grants-2016_09
Patent number
US09447090B2

Linked notes

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