Trifluoroacetic anhydride → 1-(4-methoxybenzyl)-3,4-dihydropyridin-2(1H)-one

HRID 596129Notes

Reaction equation

HRID 596129 reaction equation
[CH3:1][O:2][C:3]1[CH:17]=[CH:16][C:6]([CH2:7][N:8]2[C:13](=O)[CH2:12][CH2:11][CH2:10][C:9]2=[O:15])=[CH:5][CH:4]=1.CCC(C)[BH-](C(C)CC)C(C)CC.[Li+].CCN(C(C)C)C(C)C.C(OC(C(F)(F)F)=O)(C(F)(F)F)=O>C1(C)C=CC=CC=1.CN(C1C=CN=CC=1)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[CH:13]=[CH:12][CH2:11][CH2:10][C:9]2=[O:15])=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 9845Trifluoroacetic anhydrideHCID 81531DiisopropylethylamineHCID 3611392Lithium tri-s-butylborohydrideHCID 665869941-[(4-Methoxyphenyl)methyl]piperidine-2,6-dione

Product 1

HCID 1180460641-(4-methoxybenzyl)-3,4-dihydropyridin-2(1H)-oneYield 91.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1140TolueneSolvent

Conditions

Temperature
-78 °C

Procedure

1-(4-methoxybenzyl)piperidine-2,6-dione (8.99 g, 38.5 mmol) was dissolved in Toluene (Volume: 128 ml) and cooled to −78° C. L-Selectride (42.4 ml, 42.4 mmol) was added dropwise and the mixture agitated for 1 h. After 1 h, thick slurry along with precipitate observed. Reaction mixture was briefly pulled outside cooling bath to homogenize the mixture. Then DMAP (0.047 g, 0.385 mmol) was added in one portion and then DIEA (38.4 ml, 220 mmol) was added and then TFAA (6.53 ml, 46.2 mmol) was added. Then the cooling flask was removed and the mixture agitated at room temperature for 2 h and then quenched with water and the product extracted with EtOAc. The combined organic layer was dried (MgSO4), filtered and concentrated in vacuo to afford crude residue which was purified by flash chromatography to afford 7.66 g of the desired product as a yellow syrup. LCMS (m/z): (MH+), 234.2, 0.73 min.

Workup

  1. waitAfter 1 h
  2. customReaction mixture
  3. temperatureoutside cooling bath
  4. stirringto homogenize the mixture
  5. customThen the cooling flask was removed
  6. stirringthe mixture agitated at room temperature for 2 h
  7. customquenched with water
  8. extractionthe product extracted with EtOAc
  9. dry with materialThe combined organic layer was dried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto afford crude residue which
  13. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-21e14d927a214ac58ab182f5f5d414de
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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