Ethyl Acetate → HCID 19611596, compound

HRID 1602357Notes

Reaction equation

HRID 1602357 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][NH2:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:25]([C:27]1[CH:40]=[CH:39][C:30]([CH2:31][N:32]2[C:36]([CH:37]=O)=[CH:35][N:34]=[CH:33]2)=[CH:29][CH:28]=1)#[N:26].CCOC(C)=O>ClCCCl>[C:25]([C:27]1[CH:28]=[CH:29][C:30]([CH2:31][N:32]2[C:36]([CH2:37][NH:10][CH2:9][CH2:8][CH2:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[CH:35][N:34]=[CH:33]2)=[CH:39][CH:40]=1)#[N:26]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 162593-PhenylpropylamineHCID 5049666Sodium triacetoxyborohydrideHCID 106322894-[(5-Formylimidazol-1-yl)methyl]benzonitrile

Product 1

HCID 19611596HCID 19611596, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 3-phenylpropylamine (0.202 mL, 1.42 mmol) in 5 mL of 1,2-dichloroethane at 0° C. was added 4Å powdered molecular sieves (0.38 g), followed by sodium triacetoxyborohydride (301 mg, 1.42 mmol g). The aldehyde 6 from Step 5 of Example 1 (200 mg, 0.947 mmol) was added, and the reaction was allowed to warm to room temperature. After 2 days, the reaction was poured into EtOAc, washed with sat. aq. NaHCO3, and the aqueous layer was extracted with EtOAc. The combined organics were washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The resulting product was taken up in 12 mL of 20% CH2Cl2 /propylamine, stirred for 12 hours, concentrated in vacuo, and purified by preparative HPLC. Thus, the product was taken up in water/MeOH solution and was injected directly onto a Delta-Pak (C-18, 100A, 15 mm, 40 mm×100 mm) prep HPLC column using a gradient with 0.1% trifluoroacetic acid/water and 0.1% trifluoroacetic acid/acetonitrile as solvents. A portion of the pure fractions was then partitioned between methylene chloride and water, and the organic phase was dried (Na2SO4), filtered, and concentrated in vacuo to provide the titled product 10 as a white solid.

Workup

  1. washwashed with sat. aq. NaHCO3
  2. extractionthe aqueous layer was extracted with EtOAc
  3. washThe combined organics were washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. concentrationconcentrated in vacuo
  8. custompurified by preparative HPLC
  9. customA portion of the pure fractions was then partitioned between methylene chloride and water
  10. dry with materialthe organic phase was dried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9fdc23a94e6448449bc0696499baf443
Source dataset
uspto-grants-1999_11
Patent number
US05981562

Reaction notes

Loading…