Water → 2-acetylamino-2-(5'-chloro-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-6-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)hexanoic acid, tert-butylamide

HRID 579594

Reaktionsgleichung

Reaktionsgleichung von HRID 579594
[C:1]([NH:5][C:6](=[O:29])[C:7]([NH:25][C:26](=[O:28])[CH3:27])([CH:12]1[CH2:17][CH2:16][N:15]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][N:19]=2)[CH2:14][CH2:13]1)[CH2:8][CH2:9][CH:10]=[CH2:11])([CH3:4])([CH3:3])[CH3:2].[CH3:30][C:31]1([CH3:38])[C:35]([CH3:37])([CH3:36])[O:34][BH:33][O:32]1.O>ClCCl.[Ir+].ClC1CCC=CCCC=1.C1(P(C2C=CC=CC=2)CCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([NH:5][C:6](=[O:29])[C:7]([NH:25][C:26](=[O:28])[CH3:27])([CH:12]1[CH2:13][CH2:14][N:15]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][N:19]=2)[CH2:16][CH2:17]1)[CH2:8][CH2:9][CH2:10][CH2:11][B:33]1[O:34][C:35]([CH3:37])([CH3:36])[C:31]([CH3:38])([CH3:30])[O:32]1)([CH3:2])([CH3:3])[CH3:4]

Komponenten

7

Edukt 3

HCID 962WaterHCID 27347684,4,5,5-Tetramethyl[1,3,2]dioxaborolaneHCID 680643072-Acetylamino-2-(5'-Chloro-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-hex-5-enoic acid, tert-butylamide

Produkt 1

HCID 680643092-acetylamino-2-(5'-chloro-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-6-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)hexanoic acid, tert-butylamideAusbeute 82 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 742671,2-Bis(diphenylphosphino)ethaneKatalysatorHCID 178478077HCID 178478077, VerbindungKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of 2-acetylamino-2-(5′-chloro-3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-4-yl)-hex-5-enoic acid, tert-butylamide (1.0 g, 2.38 mmol) in dichloromethane (10 mL) was treated with chloro-1,5-cyclooctadiene iridium(I) dimer (48 mg, 3 mol %) and 1,2-bis(diphenylphosphino)ethane (57 mg, 6 mol %) under an atmosphere of nitrogen. The solution was stirred at room temperature for 30 minutes and then 4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (609 mg, 0.69 mL, 4.76 mmol) was added dropwise, and the reaction was then stirred overnight at room temperature. The reaction was poured into water and extracted with ethyl acetate (3×). The combined organic phase was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Purification by flash column chromatography (silica gel, 10-40% ethyl acetate in heptane) gave the title compound as a white solid (1.07 g, 82%); 1H NMR (CDCl3, 300 MHz) δ 8.05 (d, J=2 Hz, 1H), 7.35 (dd, J1=9.0 Hz, J2=2.5 Hz, 1H), 6.96 (br s, NH, 1H), 6.53 (d, J=9.0 Hz, 1H), 5.78 (m, 1H), 5.46 (br s, NH, 1H), 4.36 (d, J=13 Hz, 1H), 4.12 (d, J=13 Hz, 1H), 2.83 (td, J1=13.5 Hz, J2=5 Hz, 1H), 2.72 (td, J1=12.5 Hz, J2=2 Hz, 2H), 2.42 (tt, J1=12 Hz, J2=3 Hz, 1H), 1.97 (s, 3H), 1.77 (m, 2H), 1.32-1.48 (m, 4H), 1.28 (s, 9H), 1.20 (s, 12H), 1.03-1.25 (m, 2H) and 0.72 (t, J=7.5 Hz, 2H); MS (+CI): m/z for C28H46BClN4O4: expected 548.3. found 549.3 (M+H)+, 571.3 (M+Na)+.

Aufarbeitung

  1. stirringthe reaction was then stirred overnight at room temperature
  2. extractionextracted with ethyl acetate (3×)
  3. washThe combined organic phase was washed with saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash column chromatography (silica gel, 10-40% ethyl acetate in heptane)

Quellen und Nachweise

ORD-Eintrag
ord-b8f3a5c69ed54f8baf05699d57e6c93b
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09040703B2

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