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:19])=[CH:15][C:12]=3[C:13]=2[N:14]=1)=[O:4].[CH3:21][Mg+].[Br-]>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]2[C:8]([OH:20])([CH3:21])[CH2:9][O:10][C:11]3[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][C:12]=3[C:13]=2[N:14]=1)=[O:4]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -70 °C
Procedure
To a stirred solution of 9-Bromo-4-oxo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester (500 mg, 1.41 mmol) in THF (20 mL) at −70° C., was added MeMgBr (1.8 M in THF, 1.57 mL, 2.82 mmol) dropwise. The reaction was stirred at −70° C. for 3 h, and then warmed to −30° C. for 1 h. The reaction mixture was quenched with saturated aqueous NH4Cl solution at −30° C. and extracted with EtOAc (20 mL×2). The combined organic layers were washed with brine, dried over Na2SO4, concentrated and purified by flash column chromatography (silica gel, EtOAc in hexane from 0 to 30%) to give 9-Bromo-4-hydroxy-4-methyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester as a yellow solid (387 mg, 74%) LC-MS (ESI & APCI): 372.2 (M+2).
Workup
- temperaturewarmed to −30° C. for 1 h
- customThe reaction mixture was quenched with saturated aqueous NH4Cl solution at −30° C.
- extractionextracted with EtOAc (20 mL×2)
- washThe combined organic layers were washed with brine
- dry with materialdried over Na2SO4
- concentrationconcentrated
- custompurified by flash column chromatography (silica gel, EtOAc in hexane from 0 to 30%)
Sources & evidence
- ORD record
- ord-f6db10218ef741e2a8e22080bade7aa5
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09034866B2
Linked notes
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