Dimethylamine → 1-[4-[[4-[2-[3-(Dimethylamino)propyl]-2H-tetrazol-5-yl]phenoxy]methyl]-2-hydroxy-3-propylphenyl]ethanone

HRID 620242Notes

Reaction equation

HRID 620242 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:19]=[N:20][N:21]([CH2:23][CH2:24][CH2:25]Br)[N:22]=3)=[CH:14][CH:13]=2)=[C:6]([CH2:27][CH2:28][CH3:29])[C:5]=1[OH:30])(=[O:3])[CH3:2].[CH3:31][NH:32][CH3:33]>C(#N)C>[CH3:31][N:32]([CH3:33])[CH2:25][CH2:24][CH2:23][N:21]1[N:20]=[N:19][C:18]([C:15]2[CH:16]=[CH:17][C:12]([O:11][CH2:10][C:7]3[CH:8]=[CH:9][C:4]([C:1](=[O:3])[CH3:2])=[C:5]([OH:30])[C:6]=3[CH2:27][CH2:28][CH3:29])=[CH:13][CH:14]=2)=[N:22]1

Participants

4

Reactant 2

HCID 674DimethylamineHCID 144581835-[(4-((4-Acetyl-3-hydroxy-2-propylphenyl)methoxy)phenyl)]-2-(3-bromopropyl)-2H-tetrazole

Product 1

HCID 144582091-[4-[[4-[2-[3-(Dimethylamino)propyl]-2H-tetrazol-5-yl]phenoxy]methyl]-2-hydroxy-3-propylphenyl]ethanoneYield 88.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
0 °C

Procedure

5-[4-((4-Acetyl-3-hydroxy-2-propylphenyl)methoxy)phenyl]-2-(3-bromopropyl)-2H-tetrazole (2.8 g, 0.006 mol) was dissolved in acetonitrile and cooled to 10 approximately 0° C. Dimethylamine (anhydrous, excess) was cooled in the reagent bottle before it was opened then added to the cool acetonitrile solution. The solution was maintained at approximately 0° C. with an ice bath while it was stirred (approximately 5 hours). The reaction mixture was then concentrated in vacuo. Water was added and the resultant solution was extracted with ethyl acetate. The ethyl acetate layers were combined, washed with water and dried over sodium sulfate. The dried ethyl acetate layers were concentrated and the resultant residue was chromatographed by HPLC (preparatoryscale, silica gel column, eluted isocratically with a mixture of 9.5 : 0.5 methylene chloride:methanol to which 0.05% of diethylamine had been added to yield 2.3 g, 88.5% yield of the title product: m.p. 89°-91° C.; n.m.r.: (300 MHz, CDCl3) δ: 1.0 (t, 2H); 1.6 (m, 2H); 2.1 (t, 2H); 2.2 (s, 6H); 2.3, (t, 2H); 2.4 (t, 2H); 2.6 (s, 3H); 2.7 (t, 2H); 4.7 (t, 2H); 5.2 (s, 2H); 7.1 (2d, 3H); 7.6 (d, 1H); 8.1 (d, 2H); 12.7 (s, 1H).

Workup

  1. temperatureThe solution was maintained at approximately 0° C. with an ice bath while it
  2. concentrationThe reaction mixture was then concentrated in vacuo
  3. additionWater was added
  4. extractionthe resultant solution was extracted with ethyl acetate
  5. washwashed with water
  6. dry with materialdried over sodium sulfate
  7. concentrationThe dried ethyl acetate layers were concentrated
  8. customthe resultant residue was chromatographed by HPLC (preparatoryscale, silica gel column
  9. washeluted isocratically with a mixture of 9.5 : 0.5 methylene chloride
  10. additionmethanol to which 0.05% of diethylamine had been added

Sources & evidence

ORD record
ord-5c9952f878c14f299c89d7be74702718
Source dataset
uspto-grants-1989_04
Patent number
US04820722

Reaction notes

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