Pyridine → methyl 5-((5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinoline-6-carbonyl)thiophene-2-carboxylate

HRID 1876916Notes

Reaction equation

HRID 1876916 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[CH:10][N:11]3[C:20]=2[CH:19]=[C:18]2[C@@:13]([CH3:32])([C@@H:14]([CH:21]([OH:31])[C:22]4[S:26][C:25]([C:27]([O:29][CH3:30])=[O:28])=[CH:24][CH:23]=4)[CH2:15][CH2:16][CH2:17]2)[CH2:12]3)=[CH:4][CH:3]=1.N1C=CC=CC=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[CH:10][N:11]3[C:20]=2[CH:19]=[C:18]2[C@@:13]([CH3:32])([C@@H:14]([C:21]([C:22]4[S:26][C:25]([C:27]([O:29][CH3:30])=[O:28])=[CH:24][CH:23]=4)=[O:31])[CH2:15][CH2:16][CH2:17]2)[CH2:12]3)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 159087TriacetoxyperiodinaneHCID 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

Product 1

HCID 67448281methyl 5-((5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinoline-6-carbonyl)thiophene-2-carboxylateYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The above 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 was dissolved in anhydrous methylene chloride (3 mL). Pyridine (0.1 mL) and then Dess-Martin periodinane (204 mg, 0.48 mmol) were added. The reaction mixture was stirred at RT for 1 hr and quenched by the addition of saturated aqueous sodium bicarbonate solution (5 mL) and saturated aqueous sodium thiosulfate solution (2.5 mL). The mixture was stirred at RT for 30 min. The aqueous layer was separated and extracted with methylene chloride (2×2 mL). The combined organic solutions were dried (Na2SO4). Silica gel flash chromatography (20-100% ethyl acetate in heptanes) gave methyl 5-((5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinoline-6-carbonyl)thiophene-2-carboxylate (113 mg, 0.25 mmol, 78% yield for steps (b)+(c)) as a solid. MS found: (M+H)+=451.1.

Workup

  1. customquenched by the addition of saturated aqueous sodium bicarbonate solution (5 mL) and saturated aqueous sodium thiosulfate solution (2.5 mL)
  2. stirringThe mixture was stirred at RT for 30 min
  3. customThe aqueous layer was separated
  4. extractionextracted with methylene chloride (2×2 mL)
  5. dry with materialThe combined organic solutions were dried (Na2SO4)

Sources & evidence

ORD record
ord-bb9fa83181b8474f909eb42eaca07fed
Source dataset
uspto-grants-2012_11
Patent number
US08309730B2

Reaction notes

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