Isopropanol → (r)-2-Butyl-3-hydroxypropionic acid (r)-alpha-methylbenzylammonium salt

HRID 271974Notes

Reaction equation

HRID 271974 reaction equation
[CH3:1][C@@H:2]([NH2:9])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(O)(C)C.[CH2:14]([CH:18]([CH2:22][OH:23])[C:19]([OH:21])=[O:20])[CH2:15][CH2:16][CH3:17]>C(OCC)(=O)C>[CH3:1][C@@H:2]([NH3+:9])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:14]([C@H:18]([CH2:22][OH:23])[C:19]([O-:21])=[O:20])[CH2:15][CH2:16][CH3:17]

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 6431891-Phenethylamine, (+)-HCID 166556012-(Hydroxymethyl)hexanoic acid

Product 1

HCID 131727187(r)-2-Butyl-3-hydroxypropionic acid (r)-alpha-methylbenzylammonium saltYield 41.8%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
62.5 °C

Procedure

A 5 L, 4-necked, round-bottomed flaks, equipped with a mechanical stirrer, digital thermometer, reflux condenser, addition funnel with nitrogen inlet-outlet, and heating mantle is charged with (R)-α-methylbenzylamine (280.7 g, 2.316 mol), isopropanol (1.9 L) and ethyl acetate (1.63 L). The solution is stirred and heated to an internal temperature at 60-65° C., and a solution of (±)-2-butyl-3-hydroxypropionic acid (4, 322.5 g, 2.206 mol) in ethyl acetate (0.2 L) is added over a period of 15 min while maintaining the internal temperature at 60-70° C. The addition funnel is washed with ethyl acetate (0.2 L) and added to the mixture. The solution is cooled to 20-25° C. over a period of 2 hours and the resulting suspension is stirred at the same temperature for an additional 5 hours. The solids are collected by filtration, washed with a mixture of ethyl acetate-isopropanol (2:1 v/v) in two equal portions of 0.5 L each, and dried at 50-53° C. (13-49 mbar) to afford crude (R)-2-butyl-3-hydroxypropionic acid (R)-α-methylbenzylammonium salt (5, 246.3 g; 41.7%); (R):(S)=94.1:5.9.

Workup

  1. customA 5 L, 4-necked, round-bottomed flaks, equipped with a mechanical stirrer
  2. temperaturedigital thermometer, reflux
  3. additioncondenser, addition funnel with nitrogen inlet-outlet
  4. temperatureheating mantle
  5. temperaturewhile maintaining the internal temperature at 60-70° C
  6. washThe addition funnel is washed with ethyl acetate (0.2 L)
  7. additionadded to the mixture
  8. temperatureThe solution is cooled to 20-25° C. over a period of 2 hours
  9. stirringthe resulting suspension is stirred at the same temperature for an additional 5 hours
  10. filtrationThe solids are collected by filtration
  11. washwashed with a mixture of ethyl acetate-isopropanol (2:1 v/v) in two equal portions of 0.5 L each
  12. customdried at 50-53° C. (13-49 mbar)

Sources & evidence

ORD record
ord-d326a94138a543018194bcd8f01411a1
Source dataset
uspto-grants-2008_11
Patent number
US07452999B2

Reaction notes

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