Tetrahydrofuran → (E)-Ethyl 2-methyl-3-(4-((E)-2-phenyl-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl) but-1-en-1-yl)phenyl)acrylate

HRID 1057176Notes

Reaction equation

HRID 1057176 reaction equation
[H-].[Na+].C(OP([CH:11]([CH3:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13])(OCC)=O)C.[C:18]1(/[C:24](/[CH2:49][CH3:50])=[C:25](\[C:41]2[CH:48]=[CH:47][C:44](C=O)=[CH:43][CH:42]=2)/[C:26]2[CH:27]=[C:28]3[C:32](=[CH:33][CH:34]=2)[N:31]([CH:35]2[CH2:40][CH2:39][CH2:38][CH2:37][O:36]2)[N:30]=[CH:29]3)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[CH2:51]1COCC1>>[CH3:51]/[C:11](=[CH:17]\[C:44]1[CH:47]=[CH:48][C:41](/[C:25](/[C:26]2[CH:27]=[C:28]3[C:32](=[CH:33][CH:34]=2)[N:31]([CH:35]2[CH2:40][CH2:39][CH2:38][CH2:37][O:36]2)[N:30]=[CH:29]3)=[C:24](\[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)/[CH2:49][CH3:50])=[CH:42][CH:43]=1)/[C:12]([O:14][CH2:15][CH3:16])=[O:13]

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 107155Triethyl 2-phosphonopropionateHCID 86663368(E)-4-(2-Phenyl-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)benzaldehyde

Product 1

HCID 66794966(E)-Ethyl 2-methyl-3-(4-((E)-2-phenyl-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl) but-1-en-1-yl)phenyl)acrylate

Conditions

Temperature
0 °C

Procedure

To a suspension of NaH (80 mg, 2 mmol, 60% dispersion in mineral oil) in THF (10 mL) at 0° C., ethyl 2-(diethoxyphosphoryl)propanoate (0.36 g, 1.5 mmol) was added. The reaction was stirred at 0° C. for 1 h, and then a THF solution of (E)-4-(2-phenyl-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)benzaldehyde (0.44 g, 1 mmol) was added. The resulting mixture was gradually warmed to room temperature and stirred overnight. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with EtOAc (2×100 mL). The combined organic layers were washed with water, brine, dried over sodium sulfate, filtered and concentrated to give the crude material as pale yellow oil. LCMS: 437 [(M-THP+H)+H]+.

Workup

  1. temperatureThe resulting mixture was gradually warmed to room temperature
  2. stirringstirred overnight
  3. customThe reaction mixture was quenched with saturated ammonium chloride solution
  4. extractionextracted with EtOAc (2×100 mL)
  5. washThe combined organic layers were washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-42566f216bc44e0abc210d1b5689f424
Source dataset
uspto-grants-2016_07
Patent number
US09399646B2

Reaction notes

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