Tetrahydrofuran → HCID 67975086, compound

HRID 1502266Notes

Reaction equation

HRID 1502266 reaction equation
[CH3:1][C:2]1[CH:3]=[N:4][N:5]([CH:7]2[CH2:12][CH2:11][CH2:10][CH2:9][O:8]2)[CH:6]=1.O1CCCC1.C([Li])CCC.[CH2:23]([Sn:27](Cl)([CH2:32][CH2:33][CH2:34][CH3:35])[CH2:28][CH2:29][CH2:30][CH3:31])[CH2:24][CH2:25][CH3:26]>CCCCCC>[CH3:1][C:2]1[CH:3]=[N:4][N:5]([CH:7]2[CH2:12][CH2:11][CH2:10][CH2:9][O:8]2)[C:6]=1[Sn:27]([CH2:28][CH2:29][CH2:30][CH3:31])([CH2:32][CH2:33][CH2:34][CH3:35])[CH2:23][CH2:24][CH2:25][CH3:26]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 15096Tributyltin ChlorideHCID 44190586HCID 44190586, compoundHCID 178418339Butyllithium

Product 1

HCID 67975086HCID 67975086, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole (0.258 g, 1.55 mmol) in tetrahydrofuran (6 mL, 70 mmol) at −78° C. was added 2.5 M of n-butyllithium in hexane (0.80 mL). The reaction was stirred at −78° C. for 50 minutes, and then tributyltin chloride (0.60 mL, 2.2 mmol) was added. The reaction was kept at −78° C. for 2 hours and then quenched with saturated aqueous NH4Cl and warmed to room temperature. The reaction mixture was diluted with more water and extracted with ethyl acetate. The organic portion was dried with MgSO4, filtered, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (40 g silica, solvent gradient: 0-50% ethyl acetate in heptanes) to yield 520.6 mg (74%) of 4-methyl-1-(tetrahydro-2H-pyran-2-yl)-5-(tributylstannyl)-1H-pyrazole. LCMS (ESI): M+H=457.2; 1H NMR (400 MHz, DMSO-d6) δ 7.31 (s, 1H), 5.11 (d, J=8.3 Hz, 1H), 3.81 (d, J=11.4 Hz, 1H), 3.59-3.48 (m, 1H), 2.23 (dd, J=20.7, 9.4 Hz, 1H), 2.04 (s, 3H), 1.97 (d, J=12.8 Hz, 1H), 1.90 (d, J=13.3 Hz, 1H), 1.48 (m, 9H), 1.30 (dd, J=14.5, 7.3 Hz, 6H), 1.20-0.97 (m, 6H), 0.86 (t, J=7.3 Hz, 9H).

Workup

  1. waitThe reaction was kept at −78° C. for 2 hours
  2. customquenched with saturated aqueous NH4Cl
  3. temperaturewarmed to room temperature
  4. additionThe reaction mixture was diluted with more water
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic portion was dried with MgSO4
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe crude product was purified via flash chromatography on silica gel (40 g silica, solvent gradient: 0-50% ethyl acetate in heptanes)

Sources & evidence

ORD record
ord-7a7a5c895868442797827118b225c873
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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