Diiodomethane → HCID 86691268, compound

HRID 2037287Notes

Reaction equation

HRID 2037287 reaction equation
F[C:2](F)(F)C(O)=O.C([Zn]CC)C.ICI.[C:16]([NH:19][C@@:20]1([C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:25][C:24](=[CH2:26])[C@@H:23]2[C@H:21]1[C@H:22]2[C:27]([O:29][CH2:30][CH3:31])=[O:28])(=[O:18])[CH3:17]>ClCCl>[C:16]([NH:19][C@@:20]1([C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:25][C:24]2([CH2:2][CH2:26]2)[C@@H:23]2[C@H:21]1[C@H:22]2[C:27]([O:29][CH2:30][CH3:31])=[O:28])(=[O:18])[CH3:17]

Participants

6

Reactant 4

HCID 6346DiiodomethaneHCID 6422Trifluoroacetic acidHCID 89716555HCID 89716555, compoundHCID 178418750HCID 178418750, compound

Product 1

HCID 86691268HCID 86691268, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Procedure

Under nitrogen, add a solution of trifluoroacetic acid (1.9 mL, 25 mmol) in dichloromethane (12.5 mL) dropwise very slowly to a cooled (ice bath) stirred solution of diethylzinc (1M in heptanes) (25 mL, 25 mmol) in dichloromethane (12.5 mL). After 10 minutes, add a solution of diiodomethane (2.01 mL, 25 mmol) in dichloromethane (12.5 mL). After 10 minutes, add a solution of diethyl (1S,2S,5R,6S)-2-acetamido-4-methylene-bicyclo[3.1.0]hexane-2,6-dicarboxylate (2.46 g, 8.3 mmol) in dichloromethane (12.5 mL). After 60 minutes remove the ice bath and leave the reaction mixture to stir overnight at room temperature. Quench the clear reaction solution by dropwise addition of the reaction mixture to 0.2M aqueous hydrochloric acid (200 mL) under vigorous stirring. After 1 hour separate the dichloromethane layer, wash with brine, dry over magnesium sulfate, filter and concentrate in vacuum to yield the required product contaminated with unreacted starting material (4.4 g). Purify by flash chromatography eluting with ethyl acetate:cyclohexane (50:50 to 100:0) to give a colorless oil (3.1 g). Purify by SFC(RT=2.48 minutes (UV, 200 nm); HPLC Column: AD-H 30 mm×250 mm 5 μm; CO2 gradient: 5% iso-propyl alcohol w/0.2% dimethylethylamine for 0.5 minutes, then 5%-27% in 2.2 minutes. Column temperature: 35° C.; pressure: 100000 kPa; flow rate: 210 mL/minute) to yield unreacted diethyl (1S,2S,5R,6S)-2-acetamido-4-methylene-bicyclo[3.1.0]hexane-2,6-dicarboxylate. (580 mg, 2.0 mmol) and title compound (1.82 g, 5.9 mmol). MS (m/z): 310 (M+1), 332 (M+23).

Workup

  1. temperaturea cooled (ice bath)
  2. waitAfter 10 minutes
  3. customAfter 60 minutes remove the ice bath
  4. customleave the reaction mixture
  5. customQuench the clear reaction solution
  6. additionby dropwise addition of the reaction mixture to 0.2M aqueous hydrochloric acid (200 mL) under vigorous stirring
  7. customAfter 1 hour separate the dichloromethane layer
  8. washwash with brine
  9. dry with materialdry over magnesium sulfate
  10. filtrationfilter
  11. concentrationconcentrate in vacuum

Sources & evidence

ORD record
ord-6aa5197315d447e1b398e6f8f1762856
Source dataset
uspto-grants-2013_11
Patent number
US08575214B2

Reaction notes

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