Triethylamine → 3-Tert-butoxycarbonylamino-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester

HRID 1675558Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1675558
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7](Br)=[CH:8][C:9]=1[NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4].C(N(CC)CC)C.[C:26]([C:30]#[CH:31])([CH3:29])([CH3:28])[CH3:27].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>CN(C=O)C.C(Cl)Cl.[Cu]I.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:31]#[C:30][C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:8][C:9]=1[NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4]

Komponenten

9

Edukt 4

HCID 8471TriethylamineHCID 135123,3-Dimethyl-1-butyneHCID 634876Binap, (A+-)-HCID 57356848Methyl 5-bromo-3-((tert-butoxycarbonyl)amino)thiophene-2-carboxylate

Produkt 1

HCID 249893453-Tert-butoxycarbonylamino-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a solution of 3-(tert-butoxycarbonyl)amino-5-bromo-thiophene-2-carboxylic acid methyl ester (4.566 g, 13.58 mmol) in dry DMF (40 mL) are added copper (I) iodide (52 mg, 0.27 mmol), Pd2 dba3 (622 mg, 0.68 mmol) and triethylamine (9.46 mL, 67.9 mmol), and the mixture is deoxygenated by bubbling nitrogen through solution for 10 min. Then tert-butylacetylene (6.62 mL, 54.32 mmol) and BINAP (676 mg, 1.09 mmol) are added to the mixture, and it is heated at 60° C. overnight under nitrogen. The mixture is diluted with CH2Cl2 and filtered through celite washing with CH2Cl2. Filtrate is washed with brine, organic fraction is separated, dried over Na2SO4, concentrated, and the residue is purified by column chromatography on silica gel eluting with gradient of EtOAc in hexane to give of 5-(3,3-dimethyl-but-1-ynyl)-3-(tert-butoxycarbonyl)amino-thiophene-2-carboxylic acid methyl ester. 1H NMR (CDCl3) δ, ppm: 1.27 (s, 9H), 1.51 (s, 9H), 3.84 (s, 3H), 7.87 (s, 1H), 9.24 (br.s, 1H)

Aufarbeitung

  1. customthe mixture is deoxygenated
  2. customby bubbling nitrogen through solution for 10 min
  3. filtrationfiltered
  4. washthrough celite washing with CH2Cl2
  5. washFiltrate is washed with brine, organic fraction
  6. customis separated
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customthe residue is purified by column chromatography on silica gel eluting with gradient of EtOAc in hexane

Quellen und Nachweise

ORD-Eintrag
ord-9c7211bb84054280b15e9d1c70ff00c2
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003685B2

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