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

HRID 575116

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]2[C:8](=[O: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].[CH3:21][C:22]([OH:26])([C:24]#[CH:25])[CH3:23].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](=[O:20])[CH2:9][O:10][C:11]3[CH:18]=[CH:17][C:16]([C:25]#[C:24][C:22]([OH:26])([CH3:23])[CH3:21])=[CH:15][C:12]=3[C:13]=2[N:14]=1)=[O:4]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 9-Bromo-4-oxo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester (200 mg, 0.565 mmol), 2-methyl-3-butyn-2-ol (237 mg, 2.825 mmol), Pd(OAc)2 (13 mg, 0.0565 mmol), CuI (21 mg, 0.113 mmol) and PPh3 (45 mg, 0.17 mmol) in Et3N (10 mL) was degassed with N2, and the mixture was stirred at 80° C. overnight. The reaction was cooled to room temperature, concentrated and purified by flash column chromatography (silica gel, EtOAc in hexane from 0 to 30%) to give 9-(3-Hydroxy-3-methyl-but-1-ynyl)-4-oxo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester as an off-white solid (81 mg, 40%). LC-MS (ESI & APCI): 358.2 (M+1).

Workup

customwas degassed with N2
temperatureThe reaction was cooled to room temperature
concentrationconcentrated
custompurified by flash column chromatography (silica gel, EtOAc in hexane from 0 to 30%)

Sources & evidence

ORD record: ord-af41cc050d324ef6a3c77fc43b5e3380
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09034866B2

Linked notes

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