Hydrochloric Acid → HCID 68551576, compound

HRID 2359895Notes

Reaction equation

HRID 2359895 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N+:22]([O-:24])=[O:23])=[C:6]([CH:21]=1)[C:7]([NH:9][CH2:10][C:11]1[C:16]([O:17][CH3:18])=[CH:15][CH:14]=[CH:13][C:12]=1[O:19][CH3:20])=O.Cl.B>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N+:22]([O-:24])=[O:23])=[C:6]([CH2:7][NH:9][CH2:10][C:11]2[C:12]([O:19][CH3:20])=[CH:13][CH:14]=[CH:15][C:16]=2[O:17][CH3:18])[CH:21]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6331BoraneHCID 68546575HCID 68546575, compound

Product 1

HCID 68551576HCID 68551576, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

5-Chloro-N-(2,6-dimethoxybenzyl)-2-nitrobenzamide (31.3 g, 89.2 mmol) was placed in suspension in 500 mL tetrahydrofuran and the solution was heated at reflux. A mixture of borane-dimethyl sulfide complex (33.9 g, 446.2 mmol) and 50 mL tetrahydrofuran was added slowly by drops within 45 minutes to the heated reaction mixture. During the addition of the borane complex, a colorless precipitate was formed by flocculation and then went into solution again slowly after the addition was complete. The batch was heated at reflux for a total of 6 hours and stirred for 12 hours at room temperature until achieving complete conversion (TLC monitoring). The mixture was cooled to 0° C. for workup and 42 mL 2N hydrochloric acid was added slowly by drops over a period of 30 minutes, with a great evolution of gas and an increase in temperature to 10° C. due to the exothermic reaction. The reaction mixture was thawed to room temperature. According to the mass spectrometric analysis, the borane-product complex (ESI-MS [M+H+]=349.15/351.15) could not be cleaved completely to the desired product. Therefore the solids obtained after workup had to be treated again in 300 mL tetrahydrofuran with 180 mL 2N hydrochloric acid, by dropwise addition of the acid for 1 hour to the product mixture heated to 50° C. The mixture was stirred for a total of 6 hours at reflux and 12 hours at room temperature. The organic fraction, consisting mainly of tetrahydrofuran, was distilled off in vacuo, the solution was adjusted to a pH of 10 to 11 with 50% sodium hydroxide solution and extracted with dichloromethane (3×). The organic phase was dried over sodium sulfate and filtered out and the solvent was evaporated in vacuo. The isolated yellow oil was stirred into diethyl ether and a yellow precipitant of 1-(5-chloro-2-nitrophenyl)-N-(2,6-dimethoxybenzyl)-methanamine was filtered out. Yield: 19.2 g (57.0 mmol, 64%).

Workup

  1. temperaturethe solution was heated
  2. temperatureat reflux
  3. additionwas added slowly by drops within 45 minutes to the heated reaction mixture
  4. additionDuring the addition of the borane complex
  5. customa colorless precipitate was formed by flocculation
  6. additionafter the addition
  7. temperatureThe batch was heated
  8. temperatureat reflux for a total of 6 hours
  9. additionwas added slowly by drops over a period of 30 minutes, with a great evolution of gas
  10. temperaturean increase in temperature to 10° C. due to the exothermic reaction
  11. customwas thawed to room temperature

Sources & evidence

ORD record
ord-f71f55d235504a06a91bdee4caadc02e
Source dataset
uspto-grants-2014_04
Patent number
US08686002B2

Reaction notes

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