Ammonia → HCID 67253556, compound

HRID 401854Notes

Reaction equation

HRID 401854 reaction equation
N.Br.[CH2:3]([NH:6][C@@H:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9][CH:8]1[Br:16])[CH:4]=[CH2:5].Br.[CH2:18]([NH:21][C@H:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]([Br:31])[CH2:23]1)[CH:19]=[CH2:20].C#CCN[C@H]1C2C=CC=CC=2CC1>Br.O>[CH2:3]([NH:6][C@@H:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9][CH:8]1[Br:16])[CH:4]=[CH2:5].[CH2:18]([NH:21][C@H:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]([Br:31])[CH2:23]1)[CH:19]=[CH2:20]

Participants

8

Reactant 4

HCID 222AmmoniaHCID 3052776RasagilineHCID 67254977HCID 67254977, compoundHCID 67255071HCID 67255071, compound

Product 2

HCID 67253556HCID 67253556, compoundYield 15%HCID 67254701HCID 67254701, compoundYield 15%

Reagents, catalysts & solvents 2

HCID 260Hydrogen BromideSolventHCID 962WaterSolvent

Procedure

(R)-Rasagiline base pure (30 g) was dissolved in HBr (250 ml) and the solution was heated to reflux for 36 h. After the completion of reaction the mixture was cooled, diluted with water (500 ml) and slowly the solution was basified using aqueous ammonia solution. The mixture was extracted with methyl tertiary butyl ether (MTBE). The separated MTBE layer was evaporated to get a dark brown oil which exhibited 3 spots on TLC, two of which were of the desired compounds i.e., N-2-Propene-1-yl-2-bromo-(R)-aminoindan hydrobromide (Impurity A) and N-2-Propene-1-yl-3-bromo-(R)-aminoindan hydrobromide (Impurity B). The third spot had same Rf as that of the starting material i.e., the unreacted Rasagiline base. The products formed were separated by column chromatography (silica gel) using hexane-ethyl acetate mixture (75:25) as mobile phase to give pure N-2-Propene-1-yl-2-bromo-(R)-aminoindan (15% overall yield) and N-2-Propene-1-yl-3-bromo-(R)-aminoindan (15% overall yield).

Workup

  1. temperaturethe solution was heated
  2. temperatureto reflux for 36 h
  3. customAfter the completion of reaction the mixture
  4. temperaturewas cooled
  5. extractionThe mixture was extracted with methyl tertiary butyl ether (MTBE)
  6. customThe separated MTBE layer was evaporated
  7. customto get a dark brown oil which
  8. customThe products formed
  9. customwere separated by column chromatography (silica gel)

Sources & evidence

ORD record
ord-6e3fa063a1b74632b14d706e76fa6896
Source dataset
uspto-grants-2014_06
Patent number
US08741962B2

Reaction notes

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