Potassium Carbonate → HCID 89522241, compound

HRID 529733Notes

Reaction equation

HRID 529733 reaction equation
[F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]3[C@H:19]([C:22]4[C:27]([Br:28])=[CH:26][C:25](I)=[C:24]([N:30]([CH3:32])[CH3:31])[N:23]=4)[CH2:20][CH2:21][C@@H:14]23)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[C:35](B1OC(C)(C)C(C)(C)O1)([CH3:37])=[CH2:36].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]3[C@H:19]([C:22]4[C:27]([Br:28])=[CH:26][C:25]([C:35]([CH3:37])=[CH2:36])=[C:24]([N:30]([CH3:32])[CH3:31])[N:23]=4)[CH2:20][CH2:21][C@@H:14]23)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 109974264,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolaneHCID 89522300HCID 89522300, compound

Product 1

HCID 89522241HCID 89522241, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To (1R,5S,7aS)-1-[3,5-bis(trifluoromethyl)phenyl]-5-[3-bromo-6-(dimethylamino)-5-iodopyridin-2-yl]tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-3-one (50 mg, 0.075 mmol) in DMF (1 mL) was added isopropenylboronic acid pinacol ester (13.9 mg, 0.083 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (1.84 mg, 2.26 mmol) and potassium carbonate (0.5 M in water, 0.30 mL, 0.151 mmol). The system was stirred at 50° C. overnight before cooling and partitioning with water and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and concentrated before purifying by column chromatography to yield (1R,5S,7aS)-1-[3,5-bis(trifluoromethyl)phenyl]-5-[3-bromo-6-(dimethylamino)-5-(prop-1-en-2-yl)pyridin-2-yl]tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-3-one (19 mg, 0.033 mmol). MS ESI calc'd. for C24H23BrF6N3O2 [M+H]+ 580.1, found 580.2.

Workup

  1. temperaturebefore cooling
  2. custompartitioning with water and ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. custombefore purifying by column chromatography

Sources & evidence

ORD record
ord-26ffa0a1178a4272b887ae77426da9c8
Source dataset
uspto-grants-2016_05
Patent number
US09346825B2

Reaction notes

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