Methoxymethyl-triphenylphosphonium chloride → (R)-5-(3-methoxyallyl)-2,2-dimethyl-1,3-dioxolan-4-one
Reaction equation
[Cl-].[CH3:2][O:3][CH2:4][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1([Li])C=CC=CC=1.[CH3:31][C:32]1([CH3:41])[O:36][C@H:35]([CH2:37][CH:38]=O)[C:34](=[O:40])[O:33]1>CCOCC.CCOCC.C1COCC1>[CH3:2][O:3][CH:4]=[CH:38][CH2:37][C@H:35]1[O:36][C:32]([CH3:41])([CH3:31])[O:33][C:34]1=[O:40]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 0 °C
Procedure
(Conditions modified from Duttone, F. E., et. al., J. Med. Chem. 2003, 46, 2057) To a stirred solution of (methoxymethyl)triphenylphosphonium chloride (1.19 g, 3.48 mmol) in anhydrous ether (50 mL) at −10° C. under nitrogen was added phenyllithium (1.93 mL, 3.48 mmol) 1.8 M solution in diethyl ether, over 1 minute using a syringe. The mixture was stirred at 0° C. for 30 minutes and then cooled to −78° C. A solution of (R)-2-(2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl)acetaldehyde (Preparation D, Step B; 0.500 g, 3.16 mmol) in ether/THF 1:1 (50 mL) was introduced via addition funnel, and the reaction mixture was stirred at −78° C. for 1 hour and then warmed to ambient temperature and stirred for 4 hours. The crude was filtered and the residue was purified over silica gel (5-50% EtOAc in hexanes) to afford (R)-5-(3-methoxyallyl)-2,2-dimethyl-1,3-dioxolan-4-one (0.355 g, 1.90 mmol, 60% yield) as a clear, colorless oil (mixture of (E)- and (Z)-isomers).
Workup
- temperaturecooled to −78° C
- stirringthe reaction mixture was stirred at −78° C. for 1 hour
- temperaturewarmed to ambient temperature
- stirringstirred for 4 hours
- filtrationThe crude was filtered
- customthe residue was purified over silica gel (5-50% EtOAc in hexanes)
Sources & evidence
- ORD record
- ord-9b5ff0320a184f0f99fb76ee06f2332a
- Source dataset
- uspto-grants-2014_06
- Patent number
- US08754226B2
Reaction notes
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