Diisopropylethylamine → 4-Amino-3-chloro-alpha-[[[5-(2-phenylethoxy) pentyl](phenylmethyl)amino]methyl]-5-(trifluoromethyl)benzenemethanol

HRID 1032705Notes

Reaction equation

HRID 1032705 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].[C:17]1([CH2:23][CH2:24][O:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][NH:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=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:31]([CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][O:25][CH2:24][CH2:23][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=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 20062790N-[5-(2-Phenylethoxy)pentyl]benzenemethanamine

Product 1

HCID 221649154-Amino-3-chloro-alpha-[[[5-(2-phenylethoxy) pentyl](phenylmethyl)amino]methyl]-5-(trifluoromethyl)benzenemethanolYield 53.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1-[4-Amino-3-chloro-5-(trifluoromethyl)phenyl]-2-bromoethanone (0.55 g), N-[5-(2-phenylethoxy)pentyl]benzenemethanamine (0.52 g) and N,N-diisopropylethylamine (0.25 g) were stirred in tetrahydrofuran (15 ml) at room temperature under nitrogen for 40 h. The mixture was filtered and the filtrate evaporated in vacuo. The residue was dissolved in methanol (20 ml) and sodium borohydride (0.18 g) was added portionwise to the stirred solution at 0° under nitrogen. The mixture was left to stand at room temperature under nitrogen overnight, 2N hydrochloric acid (10 ml) added and the solvent evaporated in vacuo. The residue was partitioned between 8% sodium bicarbonate (100 ml) and ethyl acetate (100 ml), the organic phase separated, dried and evaporated in vacuo to give an oil. Purification by FCC on triethylamine deactivated silica (Merck 9385) eluting with cyclohexane-ethyl acetate (9:1) gave the title compound as a colourless oil (0.5 g).

Workup

  1. filtrationThe mixture was filtered
  2. customthe filtrate evaporated in vacuo
  3. dissolutionThe residue was dissolved in methanol (20 ml)
  4. additionsodium borohydride (0.18 g) was added portionwise to the stirred solution at 0° under nitrogen
  5. waitThe mixture was left
  6. addition2N hydrochloric acid (10 ml) added
  7. customthe solvent evaporated in vacuo
  8. customThe residue was partitioned between 8% sodium bicarbonate (100 ml) and ethyl acetate (100 ml)
  9. customthe organic phase separated
  10. customdried
  11. customevaporated in vacuo
  12. customto give an oil
  13. customPurification by FCC on triethylamine deactivated silica (Merck 9385)
  14. washeluting with cyclohexane-ethyl acetate (9:1)

Sources & evidence

ORD record
ord-ad88725c26284b69a46c4f162e3c3529
Source dataset
uspto-grants-1990_09
Patent number
US04959381

Reaction notes

Loading…