Pseudoephedrine → N-(2-Hydroxy-1-methyl-2-phenylethyl)-N-methyl-3-phenylpropionamide

HRID 376017

Reaction equation

HRID 376017 reaction equation
[CH3:1][C@H:2]([NH:11][CH3:12])[C@@H:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(N(CC)CC)C.[C:20](Cl)(=[O:29])[CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>O1CCCC1>[OH:10][CH:3]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH:2]([N:11]([CH3:12])[C:20](=[O:29])[CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH3:1]

Participants

5

Reactant 3

HCID 7028PseudoephedrineHCID 8471TriethylamineHCID 64801Benzenepropanoyl chloride

Product 1

HCID 53412380N-(2-Hydroxy-1-methyl-2-phenylethyl)-N-methyl-3-phenylpropionamideYield 75.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Into a dry 1 L round-bottomed flask equipped with a magnetic stirrer was added (+)-pseudoephedrine (22.34 g, 135.22 mmol, 1.0 equiv), triethylamine (21.5 mL, 154 mmol, 1.14 equiv), and tetrahydrofuran (300 mL). The solution was cooled to 0° C. and hydrocinnamoyl chloride (25.08 g, 148.74 mmol, 1.1 equiv) in tetrahydrofuran (100 mL) was added via cannula over a 20 minute interval. After 30 minutes, the reaction was quenched with water. The amide was extracted from water (1 L) with ethyl acetate (400 mL, 120 mL, 120 mL), and the combined organic extracts were dried over sodium sulfate. After removal of the solvent under reduced pressure, a white solid was obtained, which was recrystallized from 2:1:1 ether/dichloromethane/hexanes (500 mL) affording the hydrocinnamide as white crystals (30.24 g, 75% yield): mp 102°-104° C.; 1H NMR (300 MHz, C6D6) δ7.0-7.4 (m, 5H), 4.59 (br, 1H), 4.48 (t, 1H, J=7.1 Hz), 4.20 (m, 1H), 4.01 (dd, 1H, J=8.4 Hz, 2.4 Hz), 3.66 (m, 1H), 3.15 (m, 2H), 2.93 (t, 2H, J=7.7 Hz), 2.79 (s, 3H), 2.49 (m, 2H), 2.13 (m, 2H), 2.02 (s, 3H), 0.92 (d, 3H, J=7.0 Hz), 0.49 (d, 3H, J=6.8 Hz); 13C NMR (75.5 MHz, CDCl3) δ174.3, 173.2, 142.2, 141.5, 141.3, 141.1, 128.6, 128.39, 128.36, 128.31, 128.29, 128.2, 127.6, 126.8, 126.4, 126.1, 125.9, 76.3, 75.3, 58.0, 36.1, 35.4, 32.3, 31.5, 31.1, 26.9, 15.2, 14.3; FTIR (neat film) cm-1 3374 (br, m), 3027 (m), 1621 (s), 1495 (m), 1454 (m), 1406 (m), 1118(m), 1048 (m), 753 (m), 701 (m); HRMS (FAB) Calcd for C19H24NO2 (MH+): 298.1808; Found: 298.1806.

Workup

  1. customInto a dry 1 L round-bottomed flask equipped with a magnetic stirrer
  2. customthe reaction was quenched with water
  3. extractionThe amide was extracted from water (1 L) with ethyl acetate (400 mL, 120 mL, 120 mL)
  4. dry with materialthe combined organic extracts were dried over sodium sulfate
  5. customAfter removal of the solvent under reduced pressure
  6. customa white solid was obtained
  7. customwhich was recrystallized from 2:1:1 ether/dichloromethane/hexanes (500 mL)

Sources & evidence

ORD record
ord-e096ff9b784447cb8f8983ed4d9b025d
Source dataset
uspto-grants-1996_01
Patent number
US05488131

Linked notes

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