Methanol → 2,2,2-trifluoro-1-[6-hydroxy-1-(4-hydroxyphenyl)-3,4-dihydro-1H-isoquinolin-2-yl]ethanone

HRID 397077Notes

Reaction equation

HRID 397077 reaction equation
B(Br)(Br)Br.C([O:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[C:28]3[C:23](=[CH:24][C:25]([O:29]C)=[CH:26][CH:27]=3)[CH2:22][CH2:21][N:20]2[C:31](=[O:36])[C:32]([F:35])([F:34])[F:33])=[CH:15][CH:14]=1)C1C=CC=CC=1.CO>C(Cl)Cl>[F:35][C:32]([F:33])([F:34])[C:31]([N:20]1[CH2:21][CH2:22][C:23]2[C:28](=[CH:27][CH:26]=[C:25]([OH:29])[CH:24]=2)[CH:19]1[C:16]1[CH:17]=[CH:18][C:13]([OH:12])=[CH:14][CH:15]=1)=[O:36]

Participants

5

Reactant 3

HCID 887MethanolHCID 25134Boron tribromideHCID 181724231-[1-(4-Benzyloxyphenyl)-6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl]-2,2,2-trifluoroethanone

Product 1

HCID 99238782,2,2-trifluoro-1-[6-hydroxy-1-(4-hydroxyphenyl)-3,4-dihydro-1H-isoquinolin-2-yl]ethanoneYield 10%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A 1M solution of BBr3 in CH2Cl2 (6.0 ml, 6.0 mmol) was added slowly to a solution of 1-[1-(4-benzyloxyphenyl)-6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl]-2,2,2-trifluoroethanone (1.054 g, 2.4 mmol) in anhydrous CH2Cl2 (100 ml) at 0° C. under N2. The reaction mixture was warmed to rt and stirred at rt for 17 hr. MeOH (50 ml) was slowly added with stirring and the resulting solution was concentrated in vacuo to a red oil. This was dissolved in MeOH (20 ml) and 1M HCl (20 ml), and the resulting solution was stirred at rt for 4 hr, then neutralized with saturated NaHCO3 solution (60 ml). The resulting suspension was concentrated in vacuo and the remaining material was extracted with EtOAc (4×30 ml). The combined extracts were dried over MgSO4 and evaporated in vacuo to give 0.775 g of crude brown solid. Purification by flash chromatography, eluting with hexane:EtOAc (1:1) gave 0.080 g (10% yield) of white solid.

Workup

  1. stirringwith stirring
  2. concentrationthe resulting solution was concentrated in vacuo to a red oil
  3. dissolutionThis was dissolved in MeOH (20 ml)
  4. stirring1M HCl (20 ml), and the resulting solution was stirred at rt for 4 hr
  5. concentrationThe resulting suspension was concentrated in vacuo
  6. extractionthe remaining material was extracted with EtOAc (4×30 ml)
  7. dry with materialThe combined extracts were dried over MgSO4
  8. customevaporated in vacuo
  9. customto give 0.775 g of crude brown solid
  10. customPurification by flash chromatography
  11. washeluting with hexane:EtOAc (1:1)

Sources & evidence

ORD record
ord-b60b7071e9ca4f02ac9ea13f5e3b7026
Source dataset
uspto-grants-2003_08
Patent number
US06608203B2

Reaction notes

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