Acetic Acid → HCID 66797682, compound

HRID 1397595Notes

Reaction equation

HRID 1397595 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=O)[CH2:6][C:5]2([CH3:13])[CH3:12].[C:14]1([C@H:20]([CH2:22][OH:23])[NH2:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(O)(=O)C.[BH4-].[Na+]>C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C@@H:7]([NH:21][C@H:20]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:22][OH:23])[CH2:6][C:5]2([CH3:13])[CH3:12]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 825700HCID 825700, compoundHCID 2724025(R)-beta-aminophenethyl alcoholHCID 4311764Sodium borohydride

Product 1

HCID 66797682HCID 66797682, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
140 °C

Procedure

To a mixture of 5-chloro-3,3-dimethylindan-1-one (4.33 g, 0.0222 mol) and (R)-(−)-2-phenylglycinol (3.2 g, 0.0234 mol) in toluene (200 mL) was added p-toluenesulfonic acid monohydrate (241 mg, 0.00127 mol). The reaction was stirred at reflux (140° C.) under an atmosphere of nitrogen overnight, cooled and diluted with toluene. The mixture was washed with saturated aqueous NaHCO3 and water and the organic phase was concentrated. The residue was dissolved in THF (200 mL) under an atmosphere of nitrogen and cooled at 0° C. To this was added acetic acid (3.79 mL, 0.0667 mol) and sodium borohydride (1.26 g, 0.0334 mol). The reaction was stirred under at atmosphere of nitrogen overnight. The reaction was partitioned between CH2Cl2 and saturated aqueous NaHCO3 solution, separated, and the organic phase was evaporated. The residue was purified by flash chromatography (20 to 100% EtOAc/hexanes) to afford the title compound (6.25 g, 90%) as a white solid.

Workup

  1. temperaturecooled
  2. washThe mixture was washed with saturated aqueous NaHCO3 and water
  3. concentrationthe organic phase was concentrated
  4. dissolutionThe residue was dissolved in THF (200 mL) under an atmosphere of nitrogen
  5. temperaturecooled at 0° C
  6. stirringThe reaction was stirred under at atmosphere of nitrogen overnight
  7. customThe reaction was partitioned between CH2Cl2 and saturated aqueous NaHCO3 solution
  8. customseparated
  9. customthe organic phase was evaporated
  10. customThe residue was purified by flash chromatography (20 to 100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-9268af8021e74339ac35e6b79ab59788
Source dataset
uspto-grants-2014_12
Patent number
US08901136B2

Reaction notes

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