Diethylamine → Atreleuton

HRID 1720435

Reaktionsgleichung

Reaktionsgleichung von HRID 1720435
I[C:2]1[S:3][C:4]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=[CH:5][CH:6]=1.[OH:15][N:16]([C@@H:20]([C:22]#[CH:23])[CH3:21])[C:17]([NH2:19])=[O:18].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(NCC)C>CN(C=O)C.CC#N.CC#N.Cl[Pd]Cl.[Cu]I>[F:14][C:11]1[CH:12]=[CH:13][C:8]([CH2:7][C:4]2[S:3][C:2]([C:23]#[C:22][C@H:20]([N:16]([OH:15])[C:17]([NH2:19])=[O:18])[CH3:21])=[CH:6][CH:5]=2)=[CH:9][CH:10]=1

Komponenten

8

Edukt 4

HCID 8021DiethylamineHCID 11776TriphenylphosphineHCID 10558641(R)-N-hydroxy-N-(3-butyn-2-yl)ureaHCID 106154672-(4-Fluorobenzyl)-5-iodothiophene

Produkt 1

HCID 3086671AtreleutonAusbeute 18 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 6093782Bis(acetonitrile)dichloropalladiumKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 2-iodo-5-(4-fluorophenylmethyl)thiophene (5.30 g, 16.6 mmol), prepared as in step 2, in anhydrous DMF (5.0 mL) was added (R)-N-hydroxy-N-(3-butyn-2-yl)urea (2.12 g, 16.6 mmol), triphenylphosphine (84 mg, 0.32 mmol), bis(acetonitrile)palladium(II) chloride (40 mg, 0.16 mmol), copper (I) iodide (16 rag, 0.08 mmol), and diethylamine (5.6 ml). The mixture was stirred under nitrogen at ambient temperature for 22 hours and concentrated in vacuo at 32° C. The residue was subjected to chromatography on silica eluting with 2-7% MeOH in CH2Cl2, crystallization from ethyl acetate-hexane and trituration in CH2Cl2 to afford (R)-N-{3-[5-(4-fluorophenylmethyl)thien-2-yl]-1-methyl-2-propynyl}-N-hydroxyurea as a cream-colored solid 0.94 g (18%). m.p. 135°-136° C.(dec). 1H NMR (DMSO-d6, 300 MHz) δ1.32 (d, J=6.0 Hz, 3H), 4.11 (s, 2H), 5.10 (q, J=6.0Hz, 1H), 6.54 (s, 2H), 6.81 (d, J=3.0Hz, 1H), 7.08 (d, J=3.0Hz, 1H), 7.10-7.18 (m, 2H), 7.25-7.32 (m, 2H), 9.33 (s, 1H). MS (DCI/NH3) m/e 319 (M+H)+. [a]D23° =+47.8° (C=1, MeOH). Anal calcd for C16H15FN2O2S: C, 60.36; H, 4.75; N, 8.80. Found: C, 60.31; H, 4.79; N, 8.50.

Aufarbeitung

  1. concentrationconcentrated in vacuo at 32° C
  2. customThe residue was subjected to chromatography on silica eluting with 2-7% MeOH in CH2Cl2, crystallization from ethyl acetate-hexane and trituration in CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-b542e964429c4fb68f9b84c4a70fad81
Quelldatensatz
uspto-grants-1996_04
Patentnummer
US05506261

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