Acetic Acid → HCID 4025213, compound

HRID 1269376Notes

Reaction equation

HRID 1269376 reaction equation
[BH4-].[Na+].C(O)(=O)C.[C:7]1([N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[N:19]1[CH:24]=[CH:23][CH:22]=[C:21]([CH:25]=O)[CH:20]=1>C1COCC1>[C:7]1([N:13]2[CH2:18][CH2:17][N:16]([CH2:25][C:21]3[CH:20]=[N:19][CH:24]=[CH:23][CH:22]=3)[CH2:15][CH2:14]2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 70961-PhenylpiperazineHCID 103713-PyridinecarboxaldehydeHCID 4311764Sodium borohydride

Product 1

HCID 4025213HCID 4025213, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

NaBH4 (1.50 g, 38.88 mmol, 1.2 equiv.) was slowly added over 20 minutes to a solution of acetic acid (glacial, 11.13 mL, 194.41 mmol, 6 equiv.) in anhydrous THF (50 mL) at 20° C. under a nitrogen blanket with stirring at 200 RPM. After aging for another 20 minutes, pre-dried molecular sieves (3A, 45 g) and additional anhydrous THF (20 mL) were added to the reaction mixture and the stirring rate was increased to 350 RPM. Ten minutes after addition of the sieves, 1-phenylpiperazine (4, 5.00 mL, 32.40 mmol, 1 eq.) and 3-pyridinecarboxaldehyde (2, 3.74 mL, 38.88 mmol, 1.2 equiv.) were added, and the mixture aged for another 30 minutes, at which point the reaction was 100% complete, as determined by monitoring the disappearance of 4 with HPLC. The molecular sieves were removed by filtration. The filtrate containing the product was quenched into brine and the pH adjusted to 7.5 to 8. The organic layer containing the product was separated and the aqueous layer discarded. The organic layer was then concentrated to dryness and the solids dissolved in hot hexanes. The desired product was then crystallized by slow cooling to 5–10° C. The resulting crystals were vacuum filtered while cold and washed with cold hexane (50 mL×2). The product was then dried under vacuum at 45° C. and 75 mm Hg pressure. The isolated yield of compound 6 (HPLC area 99.3%, mp 70.5–72.0° C.) was 90.7%.

Workup

  1. dry with materialpre-dried molecular sieves (3A, 45 g) and additional anhydrous THF (20 mL)
  2. additionwere added to the reaction mixture
  3. temperaturethe stirring rate was increased to 350 RPM
  4. additionwere added
  5. waitthe mixture aged for another 30 minutes, at which
  6. customThe molecular sieves were removed by filtration
  7. additionThe filtrate containing the product
  8. customwas quenched into brine
  9. additionThe organic layer containing the product
  10. customwas separated
  11. concentrationThe organic layer was then concentrated to dryness
  12. dissolutionthe solids dissolved in hot hexanes
  13. customThe desired product was then crystallized
  14. temperatureby slow cooling to 5–10° C
  15. filtrationfiltered while cold and
  16. washwashed with cold hexane (50 mL×2)
  17. customThe product was then dried under vacuum at 45° C.

Sources & evidence

ORD record
ord-b1d28b499d814f98a5756b9d1d38549a
Source dataset
uspto-grants-2007_04
Patent number
US07199240B2

Reaction notes

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