(4-Iodo-pyridin-3-YL)-carbamic acid tert-butyl ester → {4-[6-(3-[1,3]Dioxan-2-ylphenyl)-4-hydroxy-6-methyl-4-trifluoromethylhept-1-ynyl]pyridin-3-yl}carbamic acid tert-butyl ester

HRID 400662Notes

Reaction equation

HRID 400662 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][O:3][CH:2]1[C:7]1[CH:8]=[C:9]([C:13]([CH3:25])([CH3:24])[CH2:14][C:15]([C:20]([F:23])([F:22])[F:21])([OH:19])[CH2:16][C:17]#[CH:18])[CH:10]=[CH:11][CH:12]=1.[C:26]([O:30][C:31](=[O:40])[NH:32][C:33]1[CH:34]=[N:35][CH:36]=[CH:37][C:38]=1I)([CH3:29])([CH3:28])[CH3:27]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(N(CC)CC)C.CN(C=O)C.C(OCC)C.[Cu]I>[C:26]([O:30][C:31](=[O:40])[NH:32][C:33]1[CH:34]=[N:35][CH:36]=[CH:37][C:38]=1[C:18]#[C:17][CH2:16][C:15]([OH:19])([C:20]([F:21])([F:22])[F:23])[CH2:14][C:13]([C:9]1[CH:10]=[CH:11][CH:12]=[C:7]([CH:2]2[O:3][CH2:4][CH2:5][CH2:6][O:1]2)[CH:8]=1)([CH3:25])[CH3:24])([CH3:29])([CH3:27])[CH3:28]

Participants

8

Reactant 2

HCID 15366413(4-Iodo-pyridin-3-YL)-carbamic acid tert-butyl esterHCID 600268426-(3-[1,3]Dioxan-2-ylphenyl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol

Product 1

HCID 60026480{4-[6-(3-[1,3]Dioxan-2-ylphenyl)-4-hydroxy-6-methyl-4-trifluoromethylhept-1-ynyl]pyridin-3-yl}carbamic acid tert-butyl esterYield 54.3%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of 6-(3-[1,3]dioxan-2-ylphenyl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol (300 mg, 0.84 mmol), (4-iodopyridin-3-yl)carbamic acid tert-butyl ester (270 mg, 0.84 mmol), bis(triphenylphosphine)palladium(II) chloride catalyst (29.6 mg, 0.04 mmol) and copper (I) iodide (16 mg, 0.08 mmol) in 4 mL of anhydrous triethylamine and 1 mL of anhydrous DMF was stirred at room temperature for 12 hours. The reaction mixture was then diluted with 30 nL of diethyl ether and washed with 20 mL of aqueous saturated ammonium chloride solution and 20 mL of brine. The organic layer was dried over magnesium sulfate and concentrated in vacuo. Column chromatography over silica gel with hexanes-ethyl acetate (5:1 to 1:1) provided 250 mg of the title compound as a foam (54% yield).

Workup

  1. washwashed with 20 mL of aqueous saturated ammonium chloride solution and 20 mL of brine
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8ddf113602d244dbbbaaa83219fba1c0
Source dataset
uspto-grants-2014_06
Patent number
US08741897B2

Reaction notes

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