1-Phenethylamine → 1-Phenethylamine, (-)-

HRID 443102Notes

Reaction equation

HRID 443102 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:26][CH3:27])=[C:6]([C:8]([F:25])([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:13]=2[N+:22]([O-:24])=[O:23])[C:9]([OH:11])=[O:10])[CH:7]=1.[CH3:28][CH:29]([NH2:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>C(O)(C)C>[CH3:28][C@H:29]([NH2:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:26][CH3:27])=[C:6]([C@@:8]([F:25])([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:20])([F:21])[F:19])=[CH:14][C:13]=2[N+:22]([O-:24])=[O:23])[C:9]([OH:11])=[O:10])[CH:7]=1

Participants

5

Reactant 2

HCID 74081-PhenethylamineHCID 154087405-Chloro-alpha-fluoro-2-methoxy-alpha-[2-nitro-4-(trifluoromethyl)-phenyl]benzeneacetic acid

Product 2

HCID 758181-Phenethylamine, (-)-Yield 41%HCID 15408741(alphaS)-alpha-Fluoro-alpha-(2-methoxy-5-chlorophenyl)-2-nitro-4-(trifluoromethyl)benzeneacetic acid

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
50 °C

Procedure

A 5-L three-necked round-bottomed flask, equipped with a mechanical stirrer and thermocouple, was charged with the racemic acid of Example 4 (392.87 g, 0.964 mol) and dissolved in isopropanol (2.0 L) to afford a light yellow solution. While stirring vigorously the reaction mixture was heated to 50° C. and then (S)-(α-methylbenzylamine was added over five minutes, causing the reaction tp turn slightly green in color. Heating was discontinued and a seed crystal was preferably added. Crystallization was observed within 15 minutes. The reaction mixture was cooled to room temperature over 2 hours while stirring and then the crystals were collected by filtration and washed with isopropanol (500 mL). After drying under vacuum, 208 g of the title compound as a 1:1 salt with (S)-α-methylbenzylamine (41% yield corrected for about 9% of 2-propanol as determined by 1H NMR; about 99.9% by HPLC) was obtained as a fluffy white solid. The product was found to be 99.3% enantiomerically pure as determined by capillary electrophoresis.

Workup

  1. customA 5-L three-necked round-bottomed flask, equipped with a mechanical stirrer
  2. customto afford a light yellow solution
  3. temperatureHeating
  4. additiona seed crystal was preferably added
  5. customCrystallization
  6. temperatureThe reaction mixture was cooled to room temperature over 2 hours
  7. stirringwhile stirring
  8. filtrationthe crystals were collected by filtration
  9. washwashed with isopropanol (500 mL)

Sources & evidence

ORD record
ord-75c383ddb8c04c8f935bacc2474e9be7
Source dataset
uspto-grants-1999_04
Patent number
US05892106

Reaction notes

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