1-Diethoxyphosphorylpropan-2-one → 1-[1-(4-Isopropoxy-3-methyl-benzoyl)-4-piperidylidene]propan-2-one

HRID 1478445Notes

Reaction equation

HRID 1478445 reaction equation
C(OP([CH2:9][C:10](=[O:12])[CH3:11])(OCC)=O)C.[CH:13]([O:16][C:17]1[CH:31]=[CH:30][C:20]([C:21]([N:23]2[CH2:28][CH2:27][C:26](=O)[CH2:25][CH2:24]2)=[O:22])=[CH:19][C:18]=1[CH3:32])([CH3:15])[CH3:14]>O1CCCC1>[CH:13]([O:16][C:17]1[CH:31]=[CH:30][C:20]([C:21]([N:23]2[CH2:28][CH2:27][C:26](=[CH:9][C:10](=[O:12])[CH3:11])[CH2:25][CH2:24]2)=[O:22])=[CH:19][C:18]=1[CH3:32])([CH3:15])[CH3:14]

Participants

4

Reactant 2

HCID 140281-Diethoxyphosphorylpropan-2-oneHCID 897045931-(4-Isopropoxy-3-methyl-benzoyl)piperidin-4-one

Product 1

HCID 897045461-[1-(4-Isopropoxy-3-methyl-benzoyl)-4-piperidylidene]propan-2-oneYield 89.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To an oven dried flask was placed 60% sodium hydride in mineral oil (1.5 g, 36 mmol). To the flask was added tetrahydrofuran (90 mL) under a nitrogen atmosphere. The mixture was cooled to 0° C. and a solution of 1-diethoxyphosphorylpropan-2-one (7.1 mL, 37 mmol) in tetrahydrofuran (20 mL) was added dropwise. The mixture was stirred at 25° C. for 30 min and treated with 1-(4-isopropoxy-3-methyl-benzoyl)piperidin-4-one (10 g, 36 mmol) in tetrahydrofuran (90 mL). The mixture was stirred at 25° C. for 24 h. The reaction was quenched with saturated aqueous sodium bicarbonate and extracted with ethyl acetate (3×200 mL). The combined organics were washed with brine, dried over magnesium sulfate and evaporated. The crude product was purified on silica gel utilizing a gradient of 0-30% ethyl acetate in hexanes to afford 1-[1-(4-isopropoxy-3-methyl-benzoyl)-4-piperidylidene]propan-2-one (10.2 g) 1H NMR (400 MHz, CDCl3) δ 7.25-7.17 (m, 2H), 6.81 (d, J=8.2 Hz, 1H), 6.12 (s, 1H), 4.60-4.51 (m, 1H), 3.66 (br d, 4H), 2.95 (br s, 2H), 2.50-2.33 (m, 2H), 2.19 (s, 6H), 1.34 (d, J=6.0 Hz, 6H). ESI-MS m/z calc. 315.18, found 316.0 (M+1)+; Retention time: 2.2 minutes (3 min run).

Workup

  1. customTo an oven dried flask
  2. stirringThe mixture was stirred at 25° C. for 24 h
  3. customThe reaction was quenched with saturated aqueous sodium bicarbonate
  4. extractionextracted with ethyl acetate (3×200 mL)
  5. washThe combined organics were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. customevaporated
  8. customThe crude product was purified on silica gel utilizing a gradient of 0-30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-4ff3090528a84ab2bf92b3038e2e6807
Source dataset
uspto-grants-2016_08
Patent number
US09403839B2

Reaction notes

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