Acetonitrile → HCID 67419339, compound

HRID 2406025Notes

Reaction equation

HRID 2406025 reaction equation
[C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1([C:16]#[CH:17])[CH2:13][O:12][C:11]([CH3:15])([CH3:14])[O:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C1(P(C2CCCCC2)C2C=CC=CC=2C2[C:37]([CH:38]([CH3:40])C)=[CH:36][C:35]([CH:41]([CH3:43])C)=CC=2C(C)C)CCCCC1.[C:53](=[O:56])([O-])[O-].[Cs+].[Cs+].[C:59](#[N:61])[CH3:60]>CC#N.CC#N.Cl[Pd]Cl.O.O1CCCC1>[C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1([C:16]#[C:17][C:8]2[CH:16]=[CH:17][C:53]([O:56][CH2:40][CH2:38][CH2:37][CH2:36][CH2:35][CH2:41][CH3:43])=[C:60]([C:59]#[N:61])[CH:9]=2)[CH2:13][O:12][C:11]([CH3:15])([CH3:14])[O:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 115143851,1-Dimethylethyl N-(5-ethynyl-2,2-dimethyl-1,3-dioxan-5-yl)carbamate

Product 1

HCID 67419339HCID 67419339, compound

Reagents, catalysts & solvents 3

HCID 6093782Bis(acetonitrile)dichloropalladiumCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Reference Example compound 3-1 (836 mg), (2,2-dimethyl-5-ethynyl-1,3-dioxan-5-yl)carbamic acid t-butyl ester (482 mg) synthesized by a known method (for example, Tetrahedron vol. 57 (2001) 6531-6538), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (54 mg), bis(acetonitrile)palladium(II) dichloride (10 mg), cesium carbonate (919 mg) were stirred in a mixed solvent of acetonitrile (15 ml) and tetrahydrofuran (2 ml) at 70° C. for 4 hr. Water was added to the reaction mixture; and the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to give [2,2-dimethyl-5-(3-cyano-4-heptyloxyphenyl)ethynyl-1,3-dioxan-5-yl]carbamic acid t-butyl ester as a brown oil (493 mg). The intermediate was dissolved in ethyl acetate (5 ml), Lindlar catalyst (80 mg) was added, and the mixture was stirred overnight under a hydrogen atmosphere. The reaction mixture was filtered and concentrated and the residue was dissolved in ethanol (4 ml), 10% palladium carbon (ethylenediamine poisoning, 40 mg) was added, and the mixture was stirred at room temperature for 2.5 hr under a hydrogen atmosphere. The solution was filtrated, and the filtrate was concentrated to give the object product (182 mg).

Workup

  1. extractionand the mixture was extracted with ethyl acetate
  2. washwashed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-ef8c874d494e4396b0cd4786c2fd89f0
Source dataset
uspto-grants-2014_08
Patent number
US08809304B2

Reaction notes

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