Imidazole → (S)-3-[(4-Iodomethyl-phenyl)-(tetrahydro-pyran-2-yloxy)-methyl]-benzonitrile

HRID 1161033Notes

Reaction equation

HRID 1161033 reaction equation
O[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]([O:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[C:10]2[CH:11]=[C:12]([CH:15]=[CH:16][CH:17]=2)[C:13]#[N:14])=[CH:5][CH:4]=1.[I:25]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1C=CN=C1.S([O-])([O-])(=O)=S.[Na+].[Na+]>ClCCl>[I:25][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]([O:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[C:10]2[CH:11]=[C:12]([CH:15]=[CH:16][CH:17]=2)[C:13]#[N:14])=[CH:5][CH:4]=1

Participants

7

Reactant 5

HCID 795ImidazoleHCID 807IodineHCID 11776TriphenylphosphineHCID 24477Sodium ThiosulfateHCID 573554673-{(S)-[4-(Hydroxymethyl)phenyl][(oxan-2-yl)oxy]methyl}benzonitrile

Product 1

HCID 57884505(S)-3-[(4-Iodomethyl-phenyl)-(tetrahydro-pyran-2-yloxy)-methyl]-benzonitrileYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Add sequentially a solution of (S)-3-[(4-hydroxymethyl-phenyl)-(tetrahydro-pyran-2-yloxy)-methyl]-benzonitrile (2.0 g, 6.18 mmol) dichloromethane (20 ml) and a solution of iodine (1.72 g, 6.80 mmol) in dichloromethane (30 ml) to a cooled (0° C.) solution of triphenylphosphine (1.78 g, 6.80 mmol) and imidazole (635 mg, 9.33 mmol) in dichloromethane (20 ml). Allow to warm to room temperature, then stir for 1.5 hours. Pour the mixture into a cold (0° C.) solution of sodium thiosulfate (3.63 g, 23 mmol) in an ice/water mixture (250 g) and stir for 30 minutes. Extract the aqueous layer with dichloromethane (30 ml). Combine the organic extracts and wash with water, dry with sodium sulfate, filter and concentrate. Purify the crude product via silica chromatography eluting with 15:85 ethyl acetate:hexanes to give the title compound (2.19 g, 82%). MS (m/z). Parent ion not observed.

Workup

  1. stirringstir for 30 minutes
  2. extractionExtract the aqueous layer with dichloromethane (30 ml)
  3. washCombine the organic extracts and wash with water
  4. dry with materialdry with sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify the crude product via silica chromatography
  8. washeluting with 15:85 ethyl acetate

Sources & evidence

ORD record
ord-668ce375bcf5491a92fd37f36c766257
Source dataset
uspto-grants-2010_10
Patent number
US07816523B2

Reaction notes

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