Benzyl Bromide → HCID 44553785, compound

HRID 714397Notes

Reaction equation

HRID 714397 reaction equation
[CH2:1]([NH:8][C:9](=[O:23])[C:10]1[CH:15]=[CH:14][N:13]=[C:12]([N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][C:17]2=[O:22])[CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:34](Br)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>O1CCCC1>[CH2:1]([NH:8][C:9](=[O:23])[C:10]1[CH:15]=[CH:14][N:13]=[C:12]([N:16]2[CH2:21][CH2:20][CH2:19][CH:18]([CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:17]2=[O:22])[CH:11]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 2733832Lithium HexamethyldisilazideHCID 58247780HCID 58247780, compound

Product 1

HCID 44553785HCID 44553785, compoundYield 33.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a solution of N-benzyl-2-(2-oxopiperidin-1-yl)isonicotinamide (0.14 g, 0.45 mmol) in anhydrous tetrahydrofuran (15 mL) was added a solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (0.52 mL, 0.45 mmol) at −78° C. under nitrogen atmosphere. The resulting solution was stirred for 30 minutes at −78° C., followed by the addition of a solution of benzyl bromide (0.15 g, 0.90 mmol) in anhydrous tetrahydrofuran (5 mL) dropwise at −78° C. The reaction mixture was warmed to ambient temperature, stirred for 2 hours, quenched with aqueous saturated ammonium chloride solution (10 mL) and extracted with dichloromethane (3×20 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with 50-65% ethyl acetate in hexanes to give N-benzyl-2-(3-benzyl-2-oxopiperidin-1-yl)isonicotinamide as a colorless solid (0.06 g, 32%): 1H NMR (300 MHz, CD3OD) δ 8.61 (d, J=6.1 Hz, 1H), 7.98 (s, 1H), 7.58 (d, J=6.2 Hz, 1H), 7.42-7.12 (m, 10H), 4.58 (d, J=4.1 Hz, 2H), 2.88-2.81 (m, 2H), 2.1-1.91 (m, 4H), 1.81-1.58 (m, 3H); MS (ES+) m/z 400.5 (M+1).

Workup

  1. temperatureThe reaction mixture was warmed to ambient temperature
  2. stirringstirred for 2 hours
  3. customquenched with aqueous saturated ammonium chloride solution (10 mL)
  4. extractionextracted with dichloromethane (3×20 mL)
  5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography
  9. washeluted with 50-65% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-4ecccf3f406c438e84919a23053e950e
Source dataset
uspto-grants-2015_11
Patent number
US09187426B2

Reaction notes

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