Iodine → HCID 22004984, compound

HRID 324884Notes

Reaction equation

HRID 324884 reaction equation
[Mg].II.[CH2:4]([O:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1Br)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH:20]([C:23]1[CH:28]=[C:27]([CH:29]([CH3:31])[CH3:30])[C:26]([C:32]([O:34][CH:35]([CH3:37])[CH3:36])=[O:33])=[C:25](OC)[C:24]=1[C:40]([O:42][CH:43]([CH3:45])[CH3:44])=[O:41])([CH3:22])[CH3:21]>O1CCCC1.C1C=CC=CC=1>[CH:20]([C:23]1[CH:28]=[C:27]([CH:29]([CH3:31])[CH3:30])[C:26]([C:32]([O:34][CH:35]([CH3:37])[CH3:36])=[O:33])=[C:25]([C:13]2[CH:14]=[CH:15][C:16]([F:18])=[CH:17][C:12]=2[O:11][CH2:4][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:24]=1[C:40]([O:42][CH:43]([CH3:45])[CH3:44])=[O:41])([CH3:21])[CH3:22]

Participants

7

Reactant 4

HCID 807Iodine2×HCID 5462224MagnesiumHCID 192614712-(Benzyloxy)-1-bromo-4-fluorobenzeneHCID 22005183HCID 22005183, compound

Product 1

HCID 22004984HCID 22004984, compound

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A dry flask containing freshly ground magnesium turnings (2.88 g, 120 mmol) and a crystal of iodine was heated until a dark purple iodine atmosphere had formed. The flask was cooled to ambient temperature and a solution of 2-bromo-5-fluorophenyl benzyl ether (33.8 g, 120 mmol, Example 166, Step A) in dry tetrahydrofuran (60 mL) was added in several portions over 40 minutes at a rate sufficient to maintain reflux. Reflux was continued for 45 minutes, then the reaction was cooled to room temperature. This solution of Grignard reagent was transferred via syringe to a second flask containing a solution of the intermediate from Step D (11.0 g, 30.2 mmol) in dry benzene (66 mL). The reaction mixture was held at reflux for one hour, quenched with 10% aqueous hydrochloric acid (300 mL) and extracted with diethyl ether (3×300 mL). The combined extracts were dried over magnesium sulfate and concentrated in vacuo to give a brown oil which was subjected to flash column chromatography on silica (80 mm×19.5″) using a stepwise gradient elution of dichloromethane:hexanes (1:3, 1:2, 1:1, 4L each). The fractions containing the product were combined and concentrated to afford an inseparable mixture of the product and an unidentified side product in about a 1:1 ratio as a pale yellow gum (5.3 g, 33% mass balance). This material was not fully characterized and was used without further purification.

Workup

  1. customhad formed
  2. temperatureto maintain
  3. temperaturereflux
  4. temperatureReflux
  5. temperaturethe reaction was cooled to room temperature
  6. temperatureat reflux for one hour
  7. customquenched with 10% aqueous hydrochloric acid (300 mL)
  8. extractionextracted with diethyl ether (3×300 mL)
  9. dry with materialThe combined extracts were dried over magnesium sulfate
  10. concentrationconcentrated in vacuo
  11. customto give a brown oil which
  12. washa stepwise gradient elution of dichloromethane:hexanes (1:3, 1:2, 1:1, 4L each)
  13. additionThe fractions containing the product
  14. concentrationconcentrated
  15. customto afford
  16. additionan inseparable mixture of the product
  17. customwas used without further purification

Sources & evidence

ORD record
ord-a74dbff929864e03a4832a02ef9266c5
Source dataset
uspto-grants-2001_04
Patent number
US06218431B1

Reaction notes

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