Tetrahydrofuran → HCID 68181702, compound
Reaction equation
BrC1[O:3][C:4]([CH3:7])=[N:5][N:6]=1.[CH3:8][Si:9]([CH3:16])([CH3:15])[C:10]#[C:11][C:12](=[O:14])[CH3:13].[Cl-].[NH4+].[CH2:19]1COCC1>>[CH3:7][C:4]1[O:3][C:13]([C:12]([OH:14])([C:11]#[C:10][Si:9]([CH3:16])([CH3:15])[CH3:8])[CH3:19])=[N:6][N:5]=1Participants
Conditions
- Temperature
- -10 °C
Procedure
To a solution of isopropylmagnesium chloride lithium chloride complex (1.56 mL of a 1.3M solution in THF, 2.02 mmol) in dry THF (5 mL) at −15° C. under an atmosphere of nitrogen was introduced 2-bromo-5-methyl-1,3,4-oxadiazole (300 mg, 1.84 mmol). The reaction mixture was warmed to −10° C. for 30 minutes. A solution of 4-(trimethylsilyl)but-3-yn-2-one (0.37 ml, 2.21 mmol) in dry THF (5 mL) was added and the reaction mixture warmed to 0° C. for 1 hr. After further warming to RT for 30 minutes, the solution was cooled to 0° C. and saturated aqueous ammonium chloride (5 mL) introduced. The reaction mixture was extracted with DCM (3×10 mL extractions) and the combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash chromatography (Biotage, heptane/EtOAc followed by an EtOAc/MeOH gradient) furnished the title compound as an orange oil: 1H NMR (500 MHz, CDCl3) delta 0.18 (9H, s), 1.95 (3H, s), 2.57 (3H, s), 3.13 (1H, s); LC-MS: m/z=+224.95 (M+H)+.
Workup
- temperaturethe reaction mixture warmed to 0° C. for 1 hr
- temperatureAfter further warming to RT for 30 minutes
- temperaturethe solution was cooled to 0° C.
- extractionThe reaction mixture was extracted with DCM (3×10 mL extractions)
- dry with materialthe combined organic extracts were dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated in vacuo
- customPurification of the residue by flash chromatography (Biotage, heptane/EtOAc
Sources & evidence
- ORD record
- ord-b385de56affc41789111783d85a7ef93
- Source dataset
- uspto-grants-2014_12
- Patent number
- US08901313B2
Reaction notes
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