Ethyl 3-iodobenzoate → ethyl 3-(((5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)(hydroxy)methyl)benzoate

HRID 1876922Notes

Reaction equation

HRID 1876922 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6].C([Mg]Cl)(C)C.[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[N:26]=[CH:27][N:28]3[C:37]=2[CH:36]=[C:35]2[C@@:30]([CH3:40])([C@@H:31]([CH:38]=[O:39])[CH2:32][CH2:33][CH2:34]2)[CH2:29]3)=[CH:21][CH:20]=1>C1COCC1>[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[N:26]=[CH:27][N:28]3[C:37]=2[CH:36]=[C:35]2[C@@:30]([CH3:40])([C@@H:31]([CH:38]([OH:39])[C:2]4[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=4)[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:32][CH2:33][CH2:34]2)[CH2:29]3)=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 143542Ethyl 3-iodobenzoateHCID 46180541(5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinoline-6-carbaldehydeHCID 178418918HCID 178418918, compound

Product 1

HCID 67447028ethyl 3-(((5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)(hydroxy)methyl)benzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of ethyl 3-iodobenzoate (0.17 mL, 1 mmol) in anhydrous THF (2 mL) cooled in an acetonitrile-dry ice bath was added isopropylmagnesium chloride solution (2M in THF, 0.5 mL, 1 mmol) dropwise under nitrogen. The reaction mixture was stirred at the same temperature for 30 min before (5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinoline-6-carbaldehyde (Example 1g, 55 mg, 0.18 mmol) was added. The mixture was stirred in an acetonitrile-dry ice bath for 1 hr before being quenched by the addition of saturated aqueous ammonium chloride solution (3 mL) at the same temperature. The reaction mixture was extracted with ethyl acetate (3×3 mL). The combined organic solutions were dried (Na2SO4) and concentrated. Silica gel flash chromatography (25-100% ethyl acetate in heptanes, then 0-10% methanol in ethyl acetate) gave ethyl 3-(((5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)(hydroxy)methyl)benzoate as a solid.

Workup

  1. additionwas added
  2. custombefore being quenched by the addition of saturated aqueous ammonium chloride solution (3 mL) at the same temperature
  3. extractionThe reaction mixture was extracted with ethyl acetate (3×3 mL)
  4. dry with materialThe combined organic solutions were dried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-107733c00e694e678dc639f37e52e0a0
Source dataset
uspto-grants-2012_11
Patent number
US08309730B2

Reaction notes

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