Triethylamine → (1S,2S)-2-Thiophen-2-yl-cyclopropanecarboxylic acid {(R)-2-hydroxy-1-[4-(2-methyl-pentyloxy)-phenyl]-ethyl}-amide

HRID 454994Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 454994
Cl.[NH2:2][C@H:3]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH:14]([CH3:18])[CH2:15][CH2:16][CH3:17])=[CH:8][CH:7]=1)[CH2:4][OH:5].C(N(CC)CC)C.[S:26]1[CH:30]=[CH:29][CH:28]=[C:27]1[C@H:31]1[CH2:33][C@@H:32]1[C:34](Cl)=[O:35]>ClCCl>[OH:5][CH2:4][C@H:3]([NH:2][C:34]([C@H:32]1[CH2:33][C@@H:31]1[C:27]1[S:26][CH:30]=[CH:29][CH:28]=1)=[O:35])[C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH:14]([CH3:18])[CH2:15][CH2:16][CH3:17])=[CH:8][CH:7]=1

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 67073905(R)-2-Amino-2-[4-(2-methyl-pentyloxy)-phenyl]-ethanol HClHCID 86658144(1S,2S)-2-thiophen-2-yl-cyclopropanecarboxylic chloride

Produkt 1

HCID 58459796(1S,2S)-2-Thiophen-2-yl-cyclopropanecarboxylic acid {(R)-2-hydroxy-1-[4-(2-methyl-pentyloxy)-phenyl]-ethyl}-amideAusbeute 48 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a solution of (1S,2S)-2-Thiophen-2-yl-cyclopropanecarboxylic acid (0.110 g, 0.66 mmol) in dichloromethane (10 ml) in an ice-bath was added oxalyl chloride (0.58 ml, 6.60 mmol), then DMF (0.1 ml) under nitrogen. The reaction mixture was stirred for 30 minutes at 0° C. The excessive solvent was removed on ratovapor and dried under high vacuum for 2 hrs to give (1S,2S)-2-thiophen-2-yl-cyclopropanecarboxylic chloride. In a separated 50 ml round-bottom flask was charged with (R)-2-Amino-2-[4-(2-methyl-pentyloxy)-phenyl]-ethanol HCl (0.47 mmol), dichloromethane (6 ml) and triethylamine (0.31 ml, 2.35 mmol) in an ice cold bath under nitrogen. The (1S,2S)-2-Thiophen-2-yl-cyclopropanecarboxylic chloride, made freshly in dichloromethane (10 ml) was added into the reaction mixture dropwise. The final reaction mixture was stirred for 1.5 hrs at room temperature. The finished reaction was quenched with water. The organic phase was washed with brine (3×10 ml), dried over MgSO4, filtrated, concentrated in vacuum and purified via column chromatography on silica gel with a gradient of 0%-100% of ethyl acetate in hexane to give a white solid (0.088 g, 48% yield): 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.14 (m, 2H), 6.99 (dd, J=5.2, 1.1 Hz, 1H), 6.81 (m, 3 H), 6.72 (d, J=3.3 Hz, 1H), 6.14 (d, J=6.3 Hz, 1H), 4.95 (m, 1H), 3.80 (m, 2H), 3.67 (m, 2H), 2.72 (dd, J=7.1, 4.8 Hz, 1H), 2.62 (m, 1H), 1.85 (m, 1H), 1.60 (m, 2H), 1.27 (m, 5H), 0.92 (d, J=6.8 Hz, 3H), 0.83 (m, 3H); LCMS (ESI) m/e 374.2 [(M+H)+, calcd for C22H30NO3S 374.5].

Aufarbeitung

  1. additionwas added into the reaction mixture dropwise
  2. customThe final reaction mixture
  3. customThe finished reaction
  4. customwas quenched with water
  5. washThe organic phase was washed with brine (3×10 ml)
  6. dry with materialdried over MgSO4
  7. filtrationfiltrated
  8. concentrationconcentrated in vacuum
  9. custompurified via column chromatography on silica gel with a gradient of 0%-100% of ethyl acetate in hexane

Quellen und Nachweise

ORD-Eintrag
ord-feb1641085604eaca2d81080e07cb95c
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08497271B2

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