10-Bromo-9-fluoro-2,3-diiodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine → 10-Bromo-9-fluoro-2-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

HRID 575013Notes

Reaction equation

HRID 575013 reaction equation
[Br:1][C:2]1[C:3]([F:18])=[CH:4][C:5]2[O:14][CH2:13][CH2:12][N:11]3[C:7](=[N:8][C:9]([I:16])=[C:10]3I)[C:6]=2[CH:17]=1.C([Mg]Br)C>O1CCCC1>[Br:1][C:2]1[C:3]([F:18])=[CH:4][C:5]2[O:14][CH2:13][CH2:12][N:11]3[C:7](=[N:8][C:9]([I:16])=[CH:10]3)[C:6]=2[CH:17]=1

Participants

4

Reactant 2

HCID 8669304910-Bromo-9-fluoro-2,3-diiodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineHCID 178418443HCID 178418443, compound

Product 1

HCID 6831272510-Bromo-9-fluoro-2-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineYield 309.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

Into a 20-L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of 9-Bromo-8-fluoro-2,3-diiodo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene (886 g, 1.66 mol, 1.00 equiv) in tetrahydrofuran (7 L), followed by the addition of ethylmagnesium bromide (1987 mL, 1.20 equiv, 1 M) dropwise with stirring at −40° C. The resulting solution was stirred at room temperature for 30 min. This reaction was repeated for 2 times. The reaction was then quenched by the addition of 10 L of saturated aqueous NH4Cl and diluted with 24 L of tetrahydrofuran. The resulting solution was separated and the aqueous layer was extracted with 4×3 L of tetrahydrofuran. The organic layers were combined and concentrated under vacuum. The solids were collected by filtration, washed with 1)(2 L of EA and dried to afford 2100 g (crude) of 9-Bromo-8-fluoro-2-iodo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene as a brown solid.

Workup

  1. customInto a 20-L 4-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. stirringThe resulting solution was stirred at room temperature for 30 min
  4. customThe reaction was then quenched by the addition of 10 L of saturated aqueous NH4Cl
  5. additiondiluted with 24 L of tetrahydrofuran
  6. customThe resulting solution was separated
  7. extractionthe aqueous layer was extracted with 4×3 L of tetrahydrofuran
  8. concentrationconcentrated under vacuum
  9. filtrationThe solids were collected by filtration
  10. washwashed with 1)(2 L of EA
  11. customdried

Sources & evidence

ORD record
ord-c8ff6ca84c75422dab38c490719d5955
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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