Diisopropylamine → Atreleuton

HRID 52177

Reaktionsgleichung

Reaktionsgleichung von HRID 52177
[OH:1][N:2]([C@@H:6]([C:8]#[CH:9])[CH3:7])[C:3]([NH2:5])=[O:4].I[C:11]1[S:12][C:13]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)=[CH:14][CH:15]=1.C(NC(C)C)(C)C.[NH4+].[OH-]>C(OC(=O)C)(C)C.CC#N.CC#N.Cl[Pd]Cl.[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCCCCCC>[F:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][C:13]2[S:12][C:11]([C:9]#[C:8][C@H:6]([N:2]([OH:1])[C:3]([NH2:5])=[O:4])[CH3:7])=[CH:15][CH:14]=2)=[CH:18][CH:19]=1

Komponenten

10

Edukt 4

HCID 7912DiisopropylamineHCID 14923Ammonium HydroxideHCID 10558641(R)-N-hydroxy-N-(3-butyn-2-yl)ureaHCID 106154672-(4-Fluorobenzyl)-5-iodothiophene

Produkt 1

HCID 3086671AtreleutonAusbeute 64 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 11776TriphenylphosphineKatalysatorHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 6093782Bis(acetonitrile)dichloropalladiumKatalysatorHCID 7915Isopropyl AcetateLösungsmittelHCID 8900HeptaneLösungsmittel

Versuchsvorschrift

To the (R)-N-hydroxy-N-(3-butyn-2-yl)urea prepared in step 3 above was added a solution of 2-iodo-5-(4-fluorophenylmethyl)thiophene (45 mmol), in isopropylacetate, followed by diisopropylamine (10 mL, 7.2 g, 71 mmol), bis(acetonitrile)palladium(II) chloride (65 mg, 0.25 mmol), copper(I)iodide (95 mg, 0.50 mmol), and triphenylphosphine (131 mg, 0.50 mmol), and the reaction mixture was stirred under nitrogen at ambient temperature for 2 hours. The reaction mixture was poured into 20% aqueous NH4OH (200 mL) and stirred for 20 min. Heptane (300 mL) was added and the mixture was cooled in an ice-water bath and stirred for 15 min. The solid was filtered off, washed with H2O, heptane, 25% CH2Cl2 /heptane, and dried in vauco to give 10.2 g (64% yield from (S)-O-p-toluenesulfonyl-3-butyn-2-ol) of (R)-N-{3-[5-(4-fluorophenylmethyl)thien-2-yl]-1-methyl-2-propynyl)-N-hydroxyurea (98% ee by chiral HPLC). 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=6.0 Hz, 1H), 6.54 (s, 2H), 6.81 (d, J=3.0 Hz, 1H), 7.08 (d, J=3.0 Hz, 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)+. [α]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. stirringstirred for 20 min
  2. temperaturethe mixture was cooled in an ice-water bath
  3. stirringstirred for 15 min
  4. filtrationThe solid was filtered off
  5. washwashed with H2O, heptane, 25% CH2Cl2 /heptane
  6. customdried in vauco

Quellen und Nachweise

ORD-Eintrag
ord-5056873437f64447b31b2631be516faa
Quelldatensatz
uspto-grants-1997_04
Patentnummer
US05616596

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