Veratraldehyde → NGD-4715

HRID 967027Notes

Reaction equation

HRID 967027 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[N:6][C:7]=1[O:8][CH3:9].[CH3:16][O:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][C:25]=1[O:26][CH3:27])[CH:21]=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C1(C)C=CC=CC=1.C(O)(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:10]2[CH2:15][CH2:14][N:13]([CH2:21][C:20]3[CH:23]=[CH:24][C:25]([O:26][CH3:27])=[C:18]([O:17][CH3:16])[CH:19]=3)[CH2:12][CH2:11]2)=[N:6][C:7]=1[O:8][CH3:9]

Participants

6

Reactant 3

HCID 8419VeratraldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 22021958HCID 22021958, compound

Product 1

HCID 9866893NGD-4715

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 1140TolueneSolvent

Procedure

A quantity of 0.1 g (0.4 mmole, 1 eq) of 1-(5-Bromo-6-methoxy-pyridin-2-yl)-piperazine and 0.061 g (0.4 mmole, 1 eq) of 3,4-dimethoxybenzaldehyde is dissolved in 5 mL of anhydrous toluene, and 3 drops of glacial acetic acid is added. An excess of NaBH(OAc)3 is added to the solution and stirred at room temperature under a nitrogen atmosphere until no starting material is detectable by TLC. At that time the reaction is quenched with saturated aqueous NaHCO3 and extracted with ethyl acetate. The ethyl acetate extracts are dried over anhydrous MgSO4 and concentrated in vacuo. The residue is chromatographed on SiO2 with 10% CH3OH (2M NH3)/CH2Cl2 to afford 1-(5-bromo-6-methoxypyridin-2-yl)-4-(3,4-dimethoxybenzyl)piperazine (compound 1). Analysis: 1H NMR (400 MHz, DMSO): 7.71 (1H, d), 7.36 (1H, s), 7.05 (2H, m), 6.39 (1H, d), 4.38 (4H, m), 3.80 (9H, m), 3.39 (4H, m), 3.02 (2H, m). MS (LC-MS): Calculated for C19H24BrN3O3 422.32, found 436.3424.31 (M+2). II. 1-(4-Chloro-3-trifluoromethyl-phenyl)-4-[1-(3,4-dimethoxy-phenyl)-ethyl]-piperazine via Scheme B

Workup

  1. customAt that time the reaction is quenched with saturated aqueous NaHCO3
  2. extractionextracted with ethyl acetate
  3. dry with materialThe ethyl acetate extracts are dried over anhydrous MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue is chromatographed on SiO2 with 10% CH3OH (2M NH3)/CH2Cl2

Sources & evidence

ORD record
ord-2da8d5fe4f9245c5bbc8eb2e7c43a24d
Source dataset
uspto-grants-2005_10
Patent number
US06953801B2

Reaction notes

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