Nitrogen → HCID 178506361, compound

HRID 1496904Notes

Reaction equation

HRID 1496904 reaction equation
[CH2:1](OC1CCCCO1)[C:2]#[CH:3].N#N.I[C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=1.S(O)(O)(=O)=O.C[NH:31][NH2:32].C([O-])(O)=O.[Na+]>C1COCC1.O.[Cu]I.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>[F:22][C:21]([F:24])([F:23])[O:20][C:17]1[CH:18]=[CH:19][C:14]([C:3]2[CH:2]=[CH:1][NH:32][N:31]=2)=[CH:15][CH:16]=1

Participants

10

Reactant 5

HCID 947NitrogenHCID 98609Tetrahydro-2-(2-propynyloxy)-2H-pyranHCID 165286Methylhydrazine sulfateHCID 516892Sodium BicarbonateHCID 27772941-Iodo-4-(trifluoromethoxy)benzene

Product 1

HCID 178506361HCID 178506361, compoundYield 100.5%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2-(2-propynyloxy)tetrahydro-2H-pyran (69) (0.758 g, 5.41 mmol), CuI (17 mg, 0.09 mmol) and PdCl2(PPh3)2 (0.158 g, 0.023 mmol) in THF (15 mL) was purged with N2. 1-Iodo-4-(trifluoromethoxy)benzene (70) (1.30 g, 4.51 mmol) in THF (10 mL) was added, followed by a solution of methylhydrazine sulfate (1.95 g, 13.5 mmol) and NaHCO3 (2.27 g, 27 mmol) in water (25 mL). The mixture was flushed with carbon monoxide and then stirred at room temperature for 2 days under one atmosphere of carbon monoxide. The resulting mixture was partitioned between CH2Cl2 and water, the CH2Cl2 fraction was dried, and the solvent was evaporated. Column chromatography of the residue on silica gel (eluting with CH2Cl2) gave 1-methyl-5-[tetrahydro-2H-pyran-2-yloxy)methyl]-3-[4-(trifluoromethoxy)phenyl]-1H-pyrazole (71) (1.034 g, 64%) as a brown solid: mp 40-42° C.; 1H NMR (CDCl3) δ 7.78 (d, J=8.8 Hz, 2H), 7.21 (d, J=8.0 Hz, 2H), 6.51 (s, 1H), 4.75 (d, J=12.8 Hz, 1H), 4.69 (t, J=3.3 Hz, 1H), 4.57 (d, J=12.8 Hz, 1H), 3.94 (s, 3H), 3.84-3.91 (m, 1H), 3.53-3.60 (m, 1H), 1.68-1.88 (m, 2H), 1.50-1.66 (m, 4H). APCI MS m/z 357 [M+H]+.

Workup

  1. customThe mixture was flushed with carbon monoxide
  2. customThe resulting mixture was partitioned between CH2Cl2 and water
  3. dry with materialthe CH2Cl2 fraction was dried
  4. customthe solvent was evaporated

Sources & evidence

ORD record
ord-4d618082538e46fca584bd0599e980ff
Source dataset
uspto-grants-2015_12
Patent number
US09198913B2

Reaction notes

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