Water → 3-[(E)-2-Pyridin-4-yl-1-(tetrahydro-pyran-2-yloxy)-vinyl]-benzonitrile
Reaction equation
[H-].[Na+].COP([CH:9]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]#[N:24])[CH:18]=1)[O:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)(=O)OC.[N:25]1[CH:30]=[CH:29][C:28]([CH:31]=O)=[CH:27][CH:26]=1.O>C1COCC1>[N:25]1[CH:30]=[CH:29][C:28](/[CH:31]=[C:9](\[C:17]2[CH:18]=[C:19]([CH:20]=[CH:21][CH:22]=2)[C:23]#[N:24])/[O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[CH:27][CH:26]=1Participants
Procedure
Sodium hydride (2.28 g, 94.98 mmol) was added to a solution of [(3-cyano-phenyl)-(tetrahydro-pyran-2-yloxy)-methyl]phosphonic acid dimethyl ester (20.58 g, 63.3 mmol) in dry THF and the mixture was stirred at room temperature for 15′. Pyridine-4-carbaldehyde (6.78 g, 63.3 mmol) was then added and the reaction mixture was stirred at 50° C. for 3 h under nitrogen atmosphere. In order to affect completion a further addition of pyridine-4-carbaldehyde (0.68 g, 6.33 mmol) was required. Distilled water (40 ml) was slowly poured into the reaction mixture and the solvent (THF) was removed under reduced pressure. The water layer was extracted with EtOAc (3×100 ml), DCM (1×100 ml) and the organic layers were dried over Na2SO4. The filtrate was evaporated to dryness to give the crude product 3-[(E)-2-Pyridin-4-yl-1-(tetrahydro-pyran-2-yloxy)-vinyl]-benzonitrile as a brown oil (19.0 g, 62.10 mmol, 98%).
Workup
- stirringthe reaction mixture was stirred at 50° C. for 3 h under nitrogen atmosphere
- customthe solvent (THF) was removed under reduced pressure
- extractionThe water layer was extracted with EtOAc (3×100 ml), DCM (1×100 ml)
- dry with materialthe organic layers were dried over Na2SO4
- customThe filtrate was evaporated to dryness
Sources & evidence
- ORD record
- ord-64bf7a684a464bfaa0f010fa5ace7b07
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08946250B2
Reaction notes
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