1-Phenethylamine, (-)- → HCID 10685833, compound

HRID 390380Notes

Reaction equation

HRID 390380 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH:10]([OH:11])[CH:9]([C:12]([OH:14])=[O:13])[CH2:8][N:7]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:6]1)=[O:4].C1([C@@H](N)C)C=CC=CC=1.CC(O)C.CCCCCC>CO.CC#N>[CH3:1][O:2][C:3]([C@H:5]1[C@@H:10]([OH:11])[C@@H:9]([C:12]([OH:14])=[O:13])[CH2:8][N:7]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:6]1)=[O:4]

Participants

6

Reactant 3

HCID 758181-Phenethylamine, (-)-HCID 21585144Isopropanol hexaneHCID 77225813HCID 77225813, compound

Product 1

HCID 10685833HCID 10685833, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of (3R,4S,5S), and (3S,4R,5R), -N-tert-Butyloxycarbonyl-4-hydroxy-piperidine-3,5-dicarboxylic acid 3-methyl ester (96% ee) (78 g, 0.26 mol) is dissolved in MeOH (500 mL) and (S)-(−)1-phenylethylamine (33 mL, 0.26 mol) at room temperature is added. The mixture is stirred for 30 min at room temperature and concentrated under reduced pressure to provide a salt as a colorless amorphous. The resulting residue is dissolved in CH3CN (1.3 L) at 70° C. and stirred vigorously at room temperature for 20 h. A white crystalline salt is collected by filtration, washed with Et2O. After repeating the same recrystallization procedure (dissolution in CH3CN and stirring at room temperature) two or three times the resulting salt is dissolved in water, acidified to pH 3 with 5N and 1N HCl, and extracted with AcOEt. The combined organic phases are dried over Na2SO4. Concentration under reduced pressure gives enantiomeric pure (3R,4S,5S)-starting material-G as a white solid: ES-MS: M+H=304: CtRet=2.37 min. chiral HPLC: >99.9% ee, AD-H, 7.5% i-PrOH/Hexane/0.1% TFA, flow 0.75 mL/min, 210 nm, tRet=24 min

Workup

  1. additionA mixture of (3R,4S,5S), and (3S,4R,5R)
  2. concentrationconcentrated under reduced pressure
  3. customto provide a salt as a colorless amorphous
  4. stirringstirred vigorously at room temperature for 20 h
  5. filtrationA white crystalline salt is collected by filtration
  6. washwashed with Et2O
  7. customthe same recrystallization procedure (dissolution in CH3CN and stirring at room temperature) two or three times the resulting salt
  8. dissolutionis dissolved in water
  9. extractionextracted with AcOEt
  10. dry with materialThe combined organic phases are dried over Na2SO4
  11. concentrationConcentration under reduced pressure
  12. customgives enantiomeric pure (3R,4S,5S)-starting material-G as a white solid
  13. customCtRet=2.37 min. chiral HPLC
  14. customtRet=24 min

Sources & evidence

ORD record
ord-98d392e923434ebd8938132fc62e0bba
Source dataset
uspto-grants-2013_02
Patent number
US08383650B2

Reaction notes

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