2-Methyl-3-butyn-2-ol → 4-Hydroxy-9-(3-hydroxy-3-methyl-but-1-ynyl)-4-methyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester

HRID 575120Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 575120
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]2[C:8]([OH:21])([CH3:20])[CH2:9][O:10][C:11]3[CH:18]=[CH:17][C:16](Br)=[CH:15][C:12]=3[C:13]=2[N:14]=1)=[O:4].[CH3:22][C:23]([OH:27])([C:25]#[CH:26])[CH3:24].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>CCN(CC)CC.CC([O-])=O.CC([O-])=O.[Pd+2].[Cu]I>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]2[C:8]([OH:21])([CH3:20])[CH2:9][O:10][C:11]3[CH:18]=[CH:17][C:16]([C:26]#[C:25][C:23]([OH:27])([CH3:24])[CH3:22])=[CH:15][C:12]=3[C:13]=2[N:14]=1)=[O:4]

Komponenten

7

Edukt 3

HCID 82582-Methyl-3-butyn-2-olHCID 11776TriphenylphosphineHCID 866931469-Bromo-4-hydroxy-4-methyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester

Produkt 1

HCID 866931474-Hydroxy-9-(3-hydroxy-3-methyl-but-1-ynyl)-4-methyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl esterAusbeute 80,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 167845palladium(II) acetateKatalysatorHCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of 9-Bromo-4-hydroxy-4-methyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester (387 mg, 1.04 mmol), 2-methyl-3-butyn-2-ol (699 mg, 8.32 mmol), Pd(OAc)2 (23 mg, 0.104 mmol), CuI (39 mg, 0.208 mmol) and PPh3 (82 mg, 0.312 mmol) in Et3N (15 mL) was degassed with N2, and the mixture was stirred at 80° C. overnight. The reaction mixture was cooled to room temperature, concentrated and purified by flash column chromatography (silica gel, EtOAc in hexane from 0 to 50%) to give 4-Hydroxy-9-(3-hydroxy-3-methyl-but-1-ynyl)-4-methyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester as a yellow solid (312 mg, 80%). LC-MS (ESI & APCI): 374.3 (M+1).

Aufarbeitung

  1. customwas degassed with N2
  2. temperatureThe reaction mixture was cooled to room temperature
  3. concentrationconcentrated
  4. custompurified by flash column chromatography (silica gel, EtOAc in hexane from 0 to 50%)

Quellen und Nachweise

ORD-Eintrag
ord-506bd4db4a4d4515b62656af6a0bea2e
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09034866B2

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