Iodine → [2-Phenyl-3-(toluene-4-sulfonyl)-3-aza-bicyclo[3.1.0]hex-1-yl]-methanol

HRID 1295356Notes

Reaction equation

HRID 1295356 reaction equation
[C:1]1([C@H:7]2[C:11]([CH2:12][OH:13])=[CH:10][CH2:9][N:8]2[S:14]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:24]([Zn]CC)C.II.ClCI>[Cl-].[NH4+].C([Zn]CC)C.C(Cl)Cl>[C:1]1([CH:7]2[N:8]([S:14]([C:17]3[CH:18]=[CH:19][C:20]([CH3:23])=[CH:21][CH:22]=3)(=[O:16])=[O:15])[CH2:9][CH:10]3[C:11]2([CH2:12][OH:13])[CH2:24]3)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

8

Reactant 4

HCID 807IodineHCID 11644ChloroiodomethaneHCID 69336464[(S)-2-phenyl-1-(toluene-4-sulfonyl)-2,5-dihydro-1H-pyrrol-3-yl]-methanolHCID 178418750HCID 178418750, compound2×

Product 1

HCID 58907337[2-Phenyl-3-(toluene-4-sulfonyl)-3-aza-bicyclo[3.1.0]hex-1-yl]-methanolYield 98%

Reagents, catalysts & solvents 3

HCID 178418750HCID 178418750, compoundCatalystHCID 6344DichloromethaneSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a flask containing racemic Intermediate 15, one enantiomer being [(S)-2-phenyl-1-(toluene-4-sulfonyl)-2,5-dihydro-1H-pyrrol-3-yl]-methanol (19.0 g, 57.8 mmol), and methylene chloride (190 mL) at 0° C. and under nitrogen was added diethyl zinc (1.1M/toluene, 57.8 mL, 63.5 mmol) all at once via syringe. The reaction was stirred for twenty minutes and iodine (14.7 g, 57.7 mmol), another portion of diethyl zinc (1.1M/toluene, 57.7 mL, 63.5 mmol), and chloroiodomethane (8.8 mL, 121.3 mmol) were added in quick succession. The reaction was stirred at 0° C. for 3 hours at which point there was much white precipitate present. GC-MS analysis of an aliquot showed no product at this point. The nitrogen inlet was removed and replaced with a CaSO4 drying tube, a third portion of diethyl zinc (1.1M/toluene, 2.0 mL, 1.8 mmol) was added, and the reaction allowed to stir at room temperature overnight. GC-MS analysis of an aliquot showed complete conversion to product. The reaction was diluted with saturated ammonium chloride solution and the phases were separated. The organics were washed with brine, dried with sodium sulfate, filtered, and concentrated to give the title compound as a thick oil (19.4 g, 98%).

Workup

  1. customat 0° C.
  2. stirringThe reaction was stirred at 0° C. for 3 hours at which point there
  3. customThe nitrogen inlet was removed
  4. customreplaced with a CaSO4 drying tube
  5. stirringto stir at room temperature overnight
  6. customthe phases were separated
  7. washThe organics were washed with brine
  8. dry with materialdried with sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-63159c61674240cb96445f5986ab7810
Source dataset
uspto-grants-2007_07
Patent number
US07241798B2

Reaction notes

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