Hydrochloric Acid → HCID 20766264, compound

HRID 2278606Notes

Reaction equation

HRID 2278606 reaction equation
Cl.C(O[C@H](C)C([N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH:14]1[CH:22]([CH3:24])[CH3:23])=O)C1C=CC=CC=1>C(O)C>[CH:22]([CH:14]1[CH2:15][C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[NH:13]1)([CH3:24])[CH3:23]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 68281913HCID 68281913, compound

Product 1

HCID 20766264HCID 20766264, compoundYield 66.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
120 °C

Procedure

5.6 ml of concentrated hydrochloric acid are added to a solution of 1.2 g of (R)-2-benzyloxy-1-(2-isopropyl-2,3-dihydroindol-1-yl)propan-1-one in 34 ml of absolute ethanol. The reaction mixture is microwave-heated at 120° C. for 1 hour, and is then cooled to ambient temperature and concentrated to dryness under reduced pressure. The residue is cooled in an ice bath and taken up in 200 ml of water, and then alkalinized with concentrated sodium hydroxide. The mixture is extracted with 2×150 ml of dichloromethane. The organic phases are combined, washed with 150 ml of water, dried over magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. The residue is purified by chromatography on a 70 g cartridge of 15-40 μm silica, elution being carried out with a 95/5 v/v cyclohexane/ethyl acetate mixture at a flow rate of 50 ml/min, and then on a 30 g cartridge of 15-40 μm silica, elution being carried out with pure cyclohexane and then with a 98/2 cyclohexane/ethyl acetate mixture, at a flow rate of 30 ml/min. 0.40 g of (−)-2-isopropylindoline is thus obtained in the form of a colorless oil, the characteristics of which are the following:

Workup

  1. temperatureis then cooled to ambient temperature
  2. concentrationconcentrated to dryness under reduced pressure
  3. temperatureThe residue is cooled in an ice bath
  4. extractionThe mixture is extracted with 2×150 ml of dichloromethane
  5. washwashed with 150 ml of water
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure
  9. customThe residue is purified by chromatography on a 70 g cartridge of 15-40 μm silica, elution
  10. washon a 30 g cartridge of 15-40 μm silica, elution

Sources & evidence

ORD record
ord-99c437e34d39415085e9b144e612178b
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

Loading…