Sodium Hydroxide → (2R)-2-phenylpropylamine malate

HRID 420824

Reaction equation

Cl.[C:2]1([CH:8]([CH3:11])[CH2:9][NH2:10])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].[C:14]([OH:22])(=[O:21])[C@H:15]([CH2:17][C:18]([OH:20])=[O:19])[OH:16]>C(O)C>[C:14]([OH:22])(=[O:21])[CH:15]([CH2:17][C:18]([OH:20])=[O:19])[OH:16].[C:2]1([C@@H:8]([CH3:11])[CH2:9][NH2:10])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 75 °C

Procedure

Charge 2-phenyl-1-propylamine HCl (317.2 g, 1.85 moles), dry ethanol (2.0 L) and NaOH beads (75.4 g, 1.89 moles) washed with additional ethanol (500 mL) to a dry 3-L round bottom flask under nitrogen. Stir the mixture for 1.6 hours. Filter and add a solution of L-malic acid (62.0 g, 0.462 mole, 0.25 equivalents) in ethanol (320 mL) dropwise to the yellow filtrate. Heat the solution to 75° C., then stir at 75° C. for 30 minutes. Remove heat and allow the solution to cool slowly. Allow the resulting thick precipitate to stir overnight. Filter the precipitate, rinse with ethanol (325 mL) and dry under reduced pressure to afford (2R)-2-phenylpropylamine malate (147.6 g, 39.5%) as a white crystalline solid. Chiral GC analysis of the free base, 2-phenyl-1-propylamine reveals 83.2% e.e. enriched in the R-isomer. (Configuration is assigned via spectrometric comparison with commercial 2-phenyl-1-propylamine.) 1H NMR (CDCl3, 300 MHz) δ 7.32 (m, 2H), 7.21 (m, 3H), 2.86 (m, 2H), 2.75 (m, 1H), 1.25 (d, 3H, J=6.9), 1.02 (br s, 2H).

Workup

washwashed with additional ethanol (500 mL) to a dry 3-L round bottom flask under nitrogen
filtrationFilter
stirringstir at 75° C. for 30 minutes
customRemove
temperatureheat
temperatureto cool slowly
stirringto stir overnight
filtrationFilter the precipitate
washrinse with ethanol (325 mL)
customdry under reduced pressure

Sources & evidence

ORD record: ord-c1eb359aa6e64ed287963ec16ad719bb
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08097652B2

Linked notes

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