Pseudoephedrine → N-(1-Hydroxy-1-phenylprop-2-yl)-N-methyl-3-cyclohexylpropionamide

HRID 1532879Notes

Reaction equation

HRID 1532879 reaction equation
S(Cl)(Cl)=O.[CH:5]1([CH2:11][CH2:12][C:13]([OH:15])=O)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1.[CH3:16][C@H:17]([NH:26][CH3:27])[C@@H:18]([OH:25])[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl.C1COCC1>[OH:25][CH:18]([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[CH:17]([N:26]([CH3:27])[C:13](=[O:15])[CH2:12][CH2:11][CH:5]1[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]1)[CH3:16]

Participants

7

Reactant 4

HCID 7028PseudoephedrineHCID 24386Thionyl ChlorideHCID 69702Cyclohexanepropanoic acidHCID 516892Sodium Bicarbonate

Product 1

HCID 22014104N-(1-Hydroxy-1-phenylprop-2-yl)-N-methyl-3-cyclohexylpropionamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Thionyl chloride (3.5 mL, 48 mmol) was added to a solution of cyclohexanepropionic acid (5.5 mL, 32 mmol) in CH2Cl2 (60 mL). The mixture was heated at reflux for 60 min and then allowed to cool to ambient temperature and the solvent removed. The residue was redissolved in THF (50 mL) and (1R,2R) pseudoephedrine (4.8 g, 29 mmol) in THF (60 mL) was added to the reaction mixture at 0° C. After stirring for 30 min, a solution of saturated NaHCO3 was added to the mixture which was then extracted with EtOAc. The organic phase was dried (MgSO4) and concentrated. The residue was chromatographed (silica gel; EtOAc/hexanes 1:1) to afford an oil which solidified when placed in the refrigerator over night (8.2 g, 94%). MS (CI/NH3) m/z: 304 (M+H)+.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 60 min
  3. customthe solvent removed
  4. dissolutionThe residue was redissolved in THF (50 mL)
  5. extractionwas then extracted with EtOAc
  6. dry with materialThe organic phase was dried (MgSO4)
  7. concentrationconcentrated
  8. customThe residue was chromatographed (silica gel; EtOAc/hexanes 1:1)
  9. customto afford an oil which
  10. waitplaced in the refrigerator over night

Sources & evidence

ORD record
ord-8dc3e0dae8a34193a9b1e7bd443ef552
Source dataset
uspto-grants-2001_03
Patent number
US06204293B1

Reaction notes

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