Tetrahydrofuran → (R)-2-Acetamido-3-methoxy-N-(4-(3-methoxyprop-1-ynyl)benzyl)propanamide

HRID 73134

Reaktionsgleichung

Reaktionsgleichung von HRID 73134
[CH2:1]1[CH2:5][O:4][CH2:3][CH2:2]1.[C:6]([NH:9][C@H:10]([CH2:22][O:23][CH3:24])[C:11]([NH:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18](I)=[CH:17][CH:16]=1)=[O:12])(=[O:8])[CH3:7].C(N(CC)CC)C.COCC#C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.CS(C)=O.CCOC(C)=O.CCOCC>[C:6]([NH:9][C@H:10]([CH2:22][O:23][CH3:24])[C:11]([NH:13][CH2:14][C:15]1[CH:16]=[CH:17][C:18]([C:2]#[C:1][CH2:5][O:4][CH3:3])=[CH:19][CH:20]=1)=[O:12])(=[O:8])[CH3:7]

Komponenten

10

Edukt 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 693933-MethoxypropyneHCID 45486399(R)-2-acetamido-3-methoxy-N-(4-iodobenzyl)propanamide

Produkt 1

HCID 44538056(R)-2-Acetamido-3-methoxy-N-(4-(3-methoxyprop-1-ynyl)benzyl)propanamide

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 679Dimethyl SulfoxideLösungsmittelHCID 3283Diethyl EtherLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To an anhydrous THF (10 mL) solution of (R)-2-acetamido-3-methoxy-N-(4-iodobenzyl)propanamide (376 mg, 1.0 mmol), triethylamine (280 μL, 2.0 mmol), 3-methoxyprop-1-yne (125 μl, 1.5 mmol), dichlorobis(triphenylphosphine)-palladium (II) (70 mg, 0.1 mmol), and CuI (38 mg, 0.2 mmol) were sequentially added under Ar. The mixture was stirred at room temperature (4 h), and then Et2O (10 mL) added and the precipitate filtered through a Celite pad. The filtrate was concentrated in vacuo and the residue was purified by flash chromatography on silica gel with EtOAc/MeOH (9/1) as the eluant to obtain (R)-6 (260 mg, 82%) as a beige solid: Rf=0.27 (EtOAc); mp 141-142° C.; [α]27D=+ 4.4° (c 1, DMSO); IR (nujol) 3278, 3096, 1640, 1554, 1458, 1370, 1304, 1257, 1192, 1099, 966, 903, 810, 732 cm−1; 1H NMR (CDCl3) δ 2.02 (s, CH3CO), 3.37 (s, OCH3), 3.45-3.47 (m, CHH′ and OCH3), 3.78 (dd, J=4.2, 9.0 Hz, CHH′), 4.32 (s, C≡CCH2OCH3) 4.38-4.52 (m, CH2N), 4.54-4.61 (m, NC(H)CO), 6.52 (d, J=6.6 Hz, CHNH), 6.91-6.99 (br t, CH2NH), 7.19 (d, J=7.9 Hz, 2 ArH), 7.41 (d, J=7.9 Hz, 2 ArH); 13C NMR (CDCl3) δ 23.2 (CH3CO), 43.2 (CH2N), 52.5 (CHCH2), 57.7 (C≡CCH2OCH3), 59.1 (OCH3), 60.4 (C≡CCH2OCH3), 71.7 (CH2OCH3), 85.2 (C≡C), 86.0 (C≡C), 121.8, 127.3, 132.1, 138.4 (C6H4), 170.4 (2C(O)); HRMS (M+H+) (ESI+) 319.1652 [M+H+] (calcd for C17H22N2O4H+ 319.1658); Anal. Calcd. for C17H22N2O4.0.33H2O: C, 62.95; H, 7.04; N, 8.64. Found: C, 62.98; H, 6.78; N, 8.47.

Aufarbeitung

  1. filtrationthe precipitate filtered through a Celite pad
  2. concentrationThe filtrate was concentrated in vacuo
  3. customthe residue was purified by flash chromatography on silica gel with EtOAc/MeOH (9/1) as the eluant
  4. customto obtain (R)-6 (260 mg, 82%) as a beige solid

Quellen und Nachweise

ORD-Eintrag
ord-7b18b60943de4f2fa8356471fd90c14d
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08829033B2

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