4-Fluorobenzaldehyde → HCID 71060378, compound

HRID 1036734Notes

Reaction equation

HRID 1036734 reaction equation
[Li+].C[Si]([N-:6][Si](C)(C)C)(C)C.[F:11][C:12]1[CH:19]=[CH:18][C:15]([CH:16]=O)=[CH:14][CH:13]=1.C([O:22][C:23]([CH:25]1[CH2:30][CH2:29][CH2:28][N:27]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:26]1)=O)C>C1COCC1>[C:34]([O:33][C:31]([N:27]1[CH2:28][CH2:29][CH2:30][C:25]2([CH:16]([C:15]3[CH:18]=[CH:19][C:12]([F:11])=[CH:13][CH:14]=3)[NH:6][C:23]2=[O:22])[CH2:26]1)=[O:32])([CH3:37])([CH3:36])[CH3:35]

Participants

5

Reactant 3

HCID 680234-FluorobenzaldehydeHCID 3577271-Tert-butyl 3-ethyl piperidine-1,3-dicarboxylateHCID 2733832Lithium Hexamethyldisilazide2×

Product 1

HCID 71060378HCID 71060378, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of 1M LHMDS (8.55 mL, 8.55 mmol) in THF was cooled to −78° C. and to this mixture 4-fluorobenzaldehyde (839 ul, 7.77 mmol) in THF (25 mL) was added dropwise. The mixture was left to stir for 50 minutes and allowed to warm to 0° C. for 10 minutes and cooled again to −78° C. In a different flask a solution of 1M LHMDS (8.55 mL, 8.55 mmol) was cooled to −78° C. and a solution of piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (2 g, 7.77 mmol) in THF (25 mL) was added dropwise. The mixture was left to stir for 40 minutes and allowed to warm to 0° C. for 10 minutes and cooled again to −78° C. The solution of trimethylsilylenamine was added dropwise to the solution of enolate maintaining the temperature below 0° C. After the addition was complete, the reaction was left to stir for 3 hours at 0° C. and allowed to warm to room temperature overnight. The reaction was quenched with water (5 ml) and the resulting solution was extracted using ethyl acetate. The organic portion was separated, dried (MgSO4) and concentrated in vacuo to yield a yellow oil. Purification by flash chromatography on silica (80 g column) eluting with 0-100% EtOAc in iso-hexane afforded the title compound;

Workup

  1. additionwas added dropwise
  2. waitThe mixture was left
  3. temperaturecooled again to −78° C
  4. waitThe mixture was left
  5. stirringto stir for 40 minutes
  6. temperatureto warm to 0° C. for 10 minutes
  7. temperaturecooled again to −78° C
  8. additionAfter the addition
  9. waitthe reaction was left
  10. stirringto stir for 3 hours at 0° C.
  11. temperatureto warm to room temperature overnight
  12. customThe reaction was quenched with water (5 ml)
  13. extractionthe resulting solution was extracted
  14. customThe organic portion was separated
  15. dry with materialdried (MgSO4)
  16. concentrationconcentrated in vacuo
  17. customto yield a yellow oil
  18. customPurification by flash chromatography on silica (80 g column)
  19. washeluting with 0-100% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-fecb033acc55413cb7cd1816b1c82717
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

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