Ammonium Chloride → methyl 5-(((5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)(hydroxy)methyl)thiophene-2-carboxylate

HRID 1876915Notes

Reaction equation

HRID 1876915 reaction equation
I[C:2]1[S:6][C:5]([C:7]([O:9][CH3:10])=[O:8])=[CH:4][CH:3]=1.C([Mg]Cl)(C)C.[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[N:24]=[CH:25][N:26]3[C:35]=2[CH:34]=[C:33]2[C@@:28]([CH3:38])([C@@H:29]([CH:36]=[O:37])[CH2:30][CH2:31][CH2:32]2)[CH2:27]3)=[CH:19][CH:18]=1.[Cl-].[NH4+]>C1COCC1>[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[N:24]=[CH:25][N:26]3[C:35]=2[CH:34]=[C:33]2[C@@:28]([CH3:38])([C@@H:29]([CH:36]([OH:37])[C:2]4[S:6][C:5]([C:7]([O:9][CH3:10])=[O:8])=[CH:4][CH:3]=4)[CH2:30][CH2:31][CH2:32]2)[CH2:27]3)=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 13156399Methyl 5-iodothiophene-2-carboxylateHCID 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 58481754methyl 5-(((5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)(hydroxy)methyl)thiophene-2-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of the above methyl 5-iodothiophene-2-carboxylate (175 mg, 0.65 mmol) in anhydrous THF (2 mL) cooled in an acetonitrile-dry ice bath was added isopropylmagnesium chloride solution (2 M in THF, 0.32 mL, 0.64 mmol) dropwise under nitrogen. The reaction mixture was stirred at the same temperature for 40 min before (5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinoline-6-carbaldehyde (Example 1g, 100 mg, 0.32 mmol) was added. After the reaction mixture was stirred at the same temperature for 1 hr, saturated aqueous ammonium chloride solution (3 mL) was added. The mixture was extracted with ethyl acetate (3×2 mL). The combined organic solutions were dried (Na2SO4) and concentrated. Silica gel flash chromatography (50-100% ethyl acetate in heptanes then 0-20% methanol in ethyl acetate) gave methyl 5-(((5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)(hydroxy)methyl)thiophene-2-carboxylate as a solid.

Workup

  1. additionwas added
  2. extractionThe mixture was extracted with ethyl acetate (3×2 mL)
  3. dry with materialThe combined organic solutions were dried (Na2SO4)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-8d636ac63c694bf5ae04cd630967463e
Source dataset
uspto-grants-2012_11
Patent number
US08309730B2

Reaction notes

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