Dichloromethane → HCID 20594299, compound

HRID 1369607Notes

Reaction equation

HRID 1369607 reaction equation
[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:15][C@@H:14]2[C@@H:9]([CH2:10][CH2:11][C@H:12]([CH2:16][N:17]3[C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[C:20]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[N:19]=[CH:18]3)[CH2:13]2)[CH2:8][N:7]1C(OC)=O)=[O:5])[CH3:2].I[Si](C)(C)C.ClCCl>C(OCC)(=O)C.CCCCCC>[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:15][C@@H:14]2[C@@H:9]([CH2:10][CH2:11][C@H:12]([CH2:16][N:17]3[C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[C:20]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[N:19]=[CH:18]3)[CH2:13]2)[CH2:8][NH:7]1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 85247Trimethylsilyl iodideHCID 20594301HCID 20594301, compound

Product 1

HCID 20594299HCID 20594299, compoundYield 50.7%

Reagents, catalysts & solvents 1

HCID 21226206Ethyl acetate hexaneSolvent

Procedure

A solution of [3S,4aR,6S,8aR]-ethyl-6-((4,5-bis-ethoxycarbonyl-1H-imidazol-1-yl)methyl)-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate (10.55 g, 0.02138 mol), iodotrimethylsilane (21.39 g, 0.1069 mol), and dichloromethane (428 mL) was stirred for 16 hours at ambient temperature until complete as determined by tic (ethyl acetate/hexane, 2:1). The reaction mixture was concentrated to approximately 200 mL, ethanol (100 mL) was added and the resulting solution concentrated to a yellow foam. The residue was dissolved in methanol (190 mL) and stirred for 30 minutes with Amberlyst 15 resin (50 g). The resin was filtered and washed with methanol (100 mL). The product was eluted from the Amberlyst resin with 2N ammonia in methanol (2×100 mL). The filtrate was concentrated to an oil. The residue was purified by Biotage Flash 40M (dichloromethane/methanol, 19:1) to give 4.72 g of the free base of the final title compound, [3S,4aR,6S,8aR]-ethyl-6-((4,5-bis-ethoxycarbonyl-1H-imidazol-1-yl)methyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate.

Workup

  1. concentrationThe reaction mixture was concentrated to approximately 200 mL, ethanol (100 mL)
  2. additionwas added
  3. concentrationthe resulting solution concentrated to a yellow foam
  4. dissolutionThe residue was dissolved in methanol (190 mL)
  5. filtrationThe resin was filtered
  6. washwashed with methanol (100 mL)
  7. washThe product was eluted from the Amberlyst resin with 2N ammonia in methanol (2×100 mL)
  8. concentrationThe filtrate was concentrated to an oil
  9. customThe residue was purified by Biotage Flash 40M (dichloromethane/methanol, 19:1)

Sources & evidence

ORD record
ord-78700cb492214e289119ef118ad4dc04
Source dataset
uspto-grants-2003_06
Patent number
US06579886B2

Reaction notes

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