Hydrochloric Acid → HCID 20766264, compound

HRID 2278607Notes

Reaction equation

HRID 2278607 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.ClC1N=C(Cl)C=C(OC)N=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

5

Reactant 3

HCID 313Hydrochloric AcidHCID 38245092,4-Dichloro-6-methoxypyrimidineHCID 68281913HCID 68281913, compound

Product 1

HCID 20766264HCID 20766264, compoundYield 43.5%

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 diastereoisomer (2) 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 taken up in 100 ml of water and is then alkalinized with concentrated sodium hydroxide. The mixture is extracted with 2×120 ml of dichloromethane. The organic phases are combined, washed with 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 pure cyclohexane and then 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 a 98/2 cyclohexane/ethyl acetate mixture, at a flow rate of 30 ml/min. 0.26 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. extractionThe mixture is extracted with 2×120 ml of dichloromethane
  4. washwashed with water
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure
  8. customThe residue is purified by chromatography on a 70 g cartridge of 15-40 μm silica, elution
  9. washwith 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

Sources & evidence

ORD record
ord-cd459b2bb2224f13aad3fc08aebf4b4c
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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