Acetic Acid → N-isopropyl-3,3-diphenylpropan-1-amine

HRID 2190325Notes

Reaction equation

HRID 2190325 reaction equation
[C:1]1([CH:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:8][CH2:9][NH2:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:17][C:18]([CH3:20])=O.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C1COCC1>[CH:18]([NH:10][CH2:9][CH2:8][CH:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)([CH3:20])[CH3:17]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 180AcetoneHCID 796983,3-DiphenylpropylamineHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 20540373N-isopropyl-3,3-diphenylpropan-1-amineYield 90.9%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3,3-diphenylpropan-1-amine 1 (4.22 g, 20.0 mmol) in DCE (100 mL) at room temperature was added acetone (1.19 g, 20.5 mmol, 1.50 mL), acetic acid (1.21 g, 20.1 mmol, 1.15 mL), and NaBH(OAc)3 (5.98 g, 28.2 mmol). The reaction mixture was stirred at room temperature for 5 min, a significant amount of precipitate formed, THF (40 mL) was added, and stirring was continued at room temperature for 3 h. The reaction mixture was quenched with 5 M NaOH, partially concentrated, and diluted with EtOAc. The aqueous phase was extracted with EtOAc (2×) and the combined organic extracts were washed with brine (1×), dried over MgSO4, filtered, and concentrated. Purification by flash column chromatography on silica gel (eluted with 2% to 8% MeOH (2 M NH3) in DCM) gave N-isopropyl-3,3-diphenylpropan-1-amine 2 (4.60 g, 90.9% yield) as a colorless oil.

Workup

  1. customa significant amount of precipitate formed
  2. stirringstirring
  3. waitwas continued at room temperature for 3 h
  4. customThe reaction mixture was quenched with 5 M NaOH
  5. concentrationpartially concentrated
  6. additiondiluted with EtOAc
  7. extractionThe aqueous phase was extracted with EtOAc (2×)
  8. washthe combined organic extracts were washed with brine (1×)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification by flash column chromatography on silica gel (eluted with 2% to 8% MeOH (2 M NH3) in DCM)

Sources & evidence

ORD record
ord-bd26ba5928624c5fa2dc27e2a4ae3989
Source dataset
uspto-grants-2012_12
Patent number
US08324396B2

Reaction notes

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