Acrolein → HCID 22351214, compound

HRID 395362Notes

Reaction equation

HRID 395362 reaction equation
[CH2:1]([CH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:14]([CH:16]=[CH2:17])=[O:15].[C:18]1([Mg]Cl)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[OH-].[Na+]>C1CCN2C(=NCCC2)CC1.CCOC(C)=O.C1COCC1>[CH2:1]([CH:8]1[CH2:13][CH2:12][N:11]([CH2:17][CH2:16][CH:14]([OH:15])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 7847AcroleinHCID 14798Sodium HydroxideHCID 317384-BenzylpiperidineHCID 178478979HCID 178478979, compound

Product 1

HCID 22351214HCID 22351214, compoundYield 85.3%

Reagents, catalysts & solvents 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-15 °C

Procedure

To a flame-dried 3-neck flask under a N2 atmosphere with a magnetic stirring bar, 4-benzylpiperidine (5.00 mL, 28 mmol, 1 eq), DBU (42 μL, 0.28 mmol, 0.01 eq), and THF (100 mL) were added, mixed, and cooled to −15° C. using a CCl4/CO2(s) bath. Acrolein (1.87 mL, 28 mmol, 1 eq) was then syringed in slowly during 10 minutes maintaining the temp. at −15° C. After 0.5 hours at −15° C., phenylmagnesium chloride (2.0 M, 14.0 mL, 28 mmol, 1 eq) was syringed in slowly and the contents allowed to slowly warm to room temperature and then stirred for 48 h. The reaction was worked up by adding 0.1 N NaOH and EtOAc (200 mL each). The viscous magnesium salts were suction filtered through fiberglass filter paper. The layers were separated and the aqueous layer was extracted again with ethyl acetate (2×200 mL). The organic layers were combined, washed with brine (1×200 mL), dried (MgSO4) and the solvent removed in vacuo to yield 7.39 g of an amber oil. Flash chromatography in 100% ethyl actetate yielded 2.48 g of an orange oil. NMR (CDCl3) δ 7.40-7.10 (m, 10H); 4.93 (d of d, 1H, J=3,7 Hz); 3.12-2.96 (m, 2H); 2.68-2.46 (m, 4H); 2.01 (t of d, 1H, J=2, 10 Hz); 1.86-1.26 (m, 8H). ESI MS detects (M+H)+=310.

Workup

  1. additionmixed
  2. customslowly during 10 minutes
  3. temperaturemaintaining the temp
  4. customat −15° C
  5. temperatureto slowly warm to room temperature
  6. filtrationThe viscous magnesium salts were suction filtered through fiberglass
  7. filtrationfilter paper
  8. customThe layers were separated
  9. extractionthe aqueous layer was extracted again with ethyl acetate (2×200 mL)
  10. washwashed with brine (1×200 mL)
  11. dry with materialdried (MgSO4)
  12. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-5dbbc4a3bed94e8f9e66dd56cc88494d
Source dataset
uspto-grants-2003_08
Patent number
US06605623B1

Reaction notes

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