Methanol → Methyl 9-bromo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxylate

HRID 1629071Notes

Reaction equation

HRID 1629071 reaction equation
[Br:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8](I)[N:7]=3.C1(P(C2C=CC=CC=2)C2[C:37]3[O:36][C:35]4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(N(CC)CC)C.C[OH:67]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:35][O:36][C:37]([C:8]1[N:7]=[C:6]2[N:10]([CH2:11][CH2:12][O:13][C:4]3[CH:3]=[C:2]([Br:1])[CH:16]=[CH:15][C:5]=32)[CH:9]=1)=[O:67]

Participants

6

Reactant 4

HCID 887MethanolHCID 8471TriethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 582048589-Bromo-2-iodo-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine

Product 1

HCID 58204541Methyl 9-bromo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
50 °C

Procedure

8-Bromo-2-iodo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene (6.000 g, 0.01534 mol) followed by palladium acetate (0.1722 g, 0.0007672 mol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.8879 g, 0.001534 mol) were added sequentially to a dry nitrogen-filled flask. Degassed triethylamine (180 mL, 1.3 mol) and methanol (60 mL) were added, and the reaction mixture was thoroughly purged with a carbon monoxide balloon for about 3 minutes. Two carbon monoxide balloons were fixed to the flask and the reaction was heated to 50° C. for 3 hours. The reaction was purged with nitrogen, concentrated in vacuo, and dry loaded onto silica gel. The crude was purified by flash chromatography (40-100% ethyl acetate in hexanes followed by 5-15% MeOH in DCM) to give 8-Bromo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid methyl ester (4.242 g) as a light brown solid. MS(ESI+) 323.0/325.0

Workup

  1. additionwere added sequentially to a dry nitrogen-
  2. additionfilled flask
  3. customthe reaction mixture was thoroughly purged with a carbon monoxide balloon for about 3 minutes
  4. customThe reaction was purged with nitrogen
  5. concentrationconcentrated in vacuo
  6. customdry
  7. customThe crude was purified by flash chromatography (40-100% ethyl acetate in hexanes followed by 5-15% MeOH in DCM)

Sources & evidence

ORD record
ord-426c87b592284eb792940b41ebca8721
Source dataset
uspto-grants-2014_07
Patent number
US08785626B2

Reaction notes

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