Diisopropylethylamine → 4-Amino-3-chloro-alpha-[[(phenylmethyl)[6-(2-pyridinylethoxy)hexyl]amino]methyl]-5-(trifluoromethyl)benzenemethanol

HRID 1032708Notes

Reaction equation

HRID 1032708 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][C:5]([C:12](=[O:15])[CH2:13]Br)=[CH:4][C:3]=1[Cl:16].[N:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH2:23][CH2:24][O:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][NH:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(N(CC)C(C)C)(C)C>O1CCCC1>[NH2:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][C:5]([CH:12]([CH2:13][N:32]([CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][O:25][CH2:24][CH2:23][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][N:17]=2)[OH:15])=[CH:4][C:3]=1[Cl:16]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 133555211-[4-Amino-3-chloro-5-(trifluoromethyl)phenyl]-2-bromo-ethanoneHCID 19876743N-[6-[2-(2-Pyridinyl)ethoxy]hexyl]benzenemethanamine

Product 1

HCID 221649134-Amino-3-chloro-alpha-[[(phenylmethyl)[6-(2-pyridinylethoxy)hexyl]amino]methyl]-5-(trifluoromethyl)benzenemethanolYield 43.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1-[4-Amino-3-chloro-5-(trifluoromethyl)phenyl]-2-bromoethanone (2.1 g), N-[6-[2-(2-pyridinyl)ethoxy]hexyl]benzenemethanamine (2.20 g) and N,N-diisopropylethylamine (0.94 g) were stirred together in tetrahydrofuran (45 ml) for 24 h at room temperature under nitrogen. The mixture was filtered and the filtrate evaporated in vacuo. The residue was dissolved in methanol (80 ml) and sodium borohydride (0.63 g) was added portionwise to the solution at 0° under nitrogen. The mixture was stirred for 1 h and then 2N hydrochloric acid (40 ml) was added. The solvent was evaporated in vacuo, the residue partitioned between 8% sodium bicarbonate solution (150 ml) and ethyl acetate (100 ml). The organic phase was separated, and the aqueous phase re-extracted with ethyl acetate (100 ml). The combined organic extracts were dried and evaporated in vacuo to give a yellow oil. Purification by FCC eluting with toluene-ethanol-triethylamine (98:2:1) afforded the title compound as a yellow oil (1.59 g).

Workup

  1. filtrationThe mixture was filtered
  2. customthe filtrate evaporated in vacuo
  3. dissolutionThe residue was dissolved in methanol (80 ml)
  4. additionsodium borohydride (0.63 g) was added portionwise to the solution at 0° under nitrogen
  5. addition2N hydrochloric acid (40 ml) was added
  6. customThe solvent was evaporated in vacuo
  7. customthe residue partitioned between 8% sodium bicarbonate solution (150 ml) and ethyl acetate (100 ml)
  8. customThe organic phase was separated
  9. extractionthe aqueous phase re-extracted with ethyl acetate (100 ml)
  10. customThe combined organic extracts were dried
  11. customevaporated in vacuo
  12. customto give a yellow oil
  13. customPurification by FCC
  14. washeluting with toluene-ethanol-triethylamine (98:2:1)

Sources & evidence

ORD record
ord-f2cb3e9b2bbf40adb5ca28fc232a6c19
Source dataset
uspto-grants-1990_09
Patent number
US04959381

Reaction notes

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