Acetic Acid → (R)-2-(((S)-3,3-Dimethyl-2,3-dihydro-1H-inden-1-yl)amino)-2-phenylethanol

HRID 447575

Reaction equation

HRID 447575 reaction equation
[CH3:1][C:2]1([CH3:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=O)[CH2:3]1.[C:13]1([C@H:19]([CH2:21][OH:22])[NH2:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.CC(O)=O.[BH4-].[Na+]>C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH3:1][C:2]1([CH3:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C@@H:4]([NH:20][C@H:19]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:21][OH:22])[CH2:3]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 3046283,3-Dimethyl-1-indanoneHCID 2724025(R)-beta-aminophenethyl alcoholHCID 4311764Sodium borohydride

Product 1

HCID 66618252(R)-2-(((S)-3,3-Dimethyl-2,3-dihydro-1H-inden-1-yl)amino)-2-phenylethanolYield 91.8%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 3,3-dimethylindan-1-one (925 mg, 5.77 mmol) and (R)-(−)-2-phenylglycinol (893 mg, 6.51 mmol) in toluene (10.0 mL) was added p-toluenesulfonic acid monohydrate (62.5 mg, 0.328 mmol). The reaction was heated to reflux under an atmosphere of nitrogen for 90 min. At this point, the mixture was cooled and diluted with toluene (10.0 mL). The mixture was washed with saturated aqueous NaHCO3 solution and H2O. The organic layer was concentrated in vacuo and the residue was dissolved in THF (10.0 mL) and cooled to 0° C. AcOH (1.13 mL, 19.9 mmol) was added, followed by sodium borohydride (251 mg, 6.64 mmol) and the reaction was allowed to warm to 23° C. overnight. The mixture was partitioned between DCM and saturated aqueous NaHCO3 solution. The organic layer was concentrated and silica gel chromatography eluting with a gradient of 5 to 35% EtOAc in DCM afforded the title compound (1.49 g, 74%). LC/MS: Rt=1.92 min, ES+ 282 (AA standard).

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux under an atmosphere of nitrogen for 90 min
  3. temperatureAt this point, the mixture was cooled
  4. washThe mixture was washed with saturated aqueous NaHCO3 solution and H2O
  5. concentrationThe organic layer was concentrated in vacuo
  6. dissolutionthe residue was dissolved in THF (10.0 mL)
  7. temperatureto warm to 23° C. overnight
  8. customThe mixture was partitioned between DCM and saturated aqueous NaHCO3 solution
  9. concentrationThe organic layer was concentrated
  10. washsilica gel chromatography eluting with a gradient of 5 to 35% EtOAc in DCM

Sources & evidence

ORD record
ord-bc2d9f9578d0496e84365ec10dcdc6bc
Source dataset
uspto-grants-2013_07
Patent number
US08481550B2

Linked notes

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