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

HRID 376017

반응식

HRID 376017 반응식
[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]

참가 물질

5

반응물 3

HCID 7028PseudoephedrineHCID 8471TriethylamineHCID 64801Benzenepropanoyl chloride

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
0 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-e096ff9b784447cb8f8983ed4d9b025d
출처 데이터셋
uspto-grants-1996_01
특허 번호
US05488131

연결된 노트

불러오는 중…