Acetic Acid → 3-(2-(1,3-difluoropropan-2-yloxy)acetyl)dihydro-2H-pyran-4(3H)-one
Reaction equation
[O:1]1[CH2:6][CH2:5][C:4](=[O:7])[CH2:3][CH2:2]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C1COCC1.[F:23][CH2:24][CH:25]([O:28][CH2:29][C:30](Cl)=[O:31])[CH2:26][F:27].C(O)(=O)C>C1(C)C=CC=CC=1.O>[F:23][CH2:24][CH:25]([O:28][CH2:29][C:30]([CH:3]1[C:4](=[O:7])[CH2:5][CH2:6][O:1][CH2:2]1)=[O:31])[CH2:26][F:27]Participants
8
Reactant 5
Product 1
Reagents, catalysts & solvents 2
Procedure
At 0° C., the toluene (5 mL) solution of tetrahydro-4H-pyran-4-one (0.344 mL, 3.72 mmol) was treated with LiHMDS, 1M solution in THF (3.97 mL, 3.97 mmol) under N2 atmosphere. After 2 minutes 2-(1,3-difluoropropan-2-yloxy)acetyl chloride (428 mg, 2.48 mmol) in toluene (1 mL) was added. After 5 minutes, acetic acid (0.270 mL, 4.71 mmol) and 10 ml water were added. The phases were separated and the aqueous layer was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The solvent was removed in vacuo and the residual oil was purified by silica flash chromatography (EtOAc/Heptane gradient) to afford the title product (0.095 g, 16% yield).
Workup
- customThe phases were separated
- extractionthe aqueous layer was extracted with ethyl acetate
- dry with materialThe organic layer was dried over anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customThe solvent was removed in vacuo
- customthe residual oil was purified by silica flash chromatography (EtOAc/Heptane gradient)
Sources & evidence
- ORD record
- ord-4cb55cba6fc24e68811c3b86da2bb227
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08188101B2
Reaction notes
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