Triphenylphosphine → 3-nitro-1-[1-(tetrahydro-pyran-2-yloxy)-cyclopropylmethyl]-1H-pyrazole

HRID 546121Notes

Reaction equation

HRID 546121 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][C:8]1([CH2:11]O)[CH2:10][CH2:9]1.[N+:13]([C:16]1[CH:20]=[CH:19][NH:18][N:17]=1)([O-:15])=[O:14].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[N+:13]([C:16]1[CH:20]=[CH:19][N:18]([CH2:11][C:8]2([O:7][CH:2]3[CH2:3][CH2:4][CH2:5][CH2:6][O:1]3)[CH2:9][CH2:10]2)[N:17]=1)([O-:15])=[O:14]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 24976871[1-(Tetrahydro-pyran-2-yloxy)-cyclopropyl]-methanolHCID 178526745HCID 178526745, compound

Product 1

HCID 671895763-nitro-1-[1-(tetrahydro-pyran-2-yloxy)-cyclopropylmethyl]-1H-pyrazoleYield 21%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

[1-(Tetrahydro-pyran-2-yloxy)-cyclopropyl]-methanol (1.00 g, 5.81 mmol), 3-nitro-1H-pyrazole (prepared in example 3, 656 mg, 5.81 mmol), and triphenylphosphine (1.52 g, 5.81 mmol) were combined and dissolved in anhydrous tetrahydrofuran (30 mL). The reaction was chilled to 0° C. under nitrogen. While stirring, diisopropyl azodicarboxylate (1.72 mL, 8.72 mmol) was added dropwise over a period of 2 min. The ice bath was removed and the reaction continued to stir at 25° C. for 30 min. The reaction was concentrated in vacuo to give a thick golden oil. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 5% ethyl acetate/hexanes to 35% ethyl acetate/hexanes) afforded 3-nitro-1-[1-(tetrahydro-pyran-2-yloxy)-cyclopropylmethyl]-1H-pyrazole (326 mg, 21%) as a white powder: H1-NMR (400 MHz, CDCl3) δ 0.74-0.82 (1H, m), 0.86-0.94 (1H, m), 0.95-1.02 (1H, m), 1.05-1.03 (1H, m), 1.40-1.70 (5H, m), 1.74-1.84 (1H, m), 3.46-3.54 (1H, m), 3.83-3.90 (1H, m), 3.94 (1H, d, J=14.4 Hz), 4.66-4.72 (1H, m), 4.87-4.94 (1H, m), 6.88 (1H, d, J=2.8 Hz), 7.84 (1H, d, J=2.4 Hz).

Workup

  1. customThe ice bath was removed
  2. stirringto stir at 25° C. for 30 min
  3. concentrationThe reaction was concentrated in vacuo
  4. customto give a thick golden oil
  5. customPurification by flash column chromatography (Merck silica gel 60, 40-63 μm; 5% ethyl acetate/hexanes to 35% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-13e53462382c4ee2aa218d3927bb6e2d
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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