Sodium Carbonate → HCID 58406099, compound

HRID 218007Notes

Reaction equation

HRID 218007 reaction equation
[F:1][C:2]1[C:7](B(O)O)=[CH:6][CH:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].C(OC([N:24]([C:32]1[S:41][CH2:40][C@H:39]2[C@:34]([C:46]3[CH:51]=[C:50](Br)[CH:49]=[CH:48][C:47]=3[F:53])([CH2:35][O:36][C@@H:37]([C:42]([F:45])([F:44])[F:43])[CH2:38]2)[N:33]=1)C(OC(C)(C)C)=O)=O)(C)(C)C>CN(C=O)C.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:53][C:47]1[CH:48]=[CH:49][C:50]([C:7]2[C:2]([F:1])=[N:3][CH:4]=[CH:5][CH:6]=2)=[CH:51][C:46]=1[C@@:34]12[N:33]=[C:32]([NH2:24])[S:41][CH2:40][C@@H:39]1[CH2:38][C@H:37]([C:42]([F:45])([F:43])[F:44])[O:36][CH2:35]2

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 59281224HCID 59281224, compound

Product 1

HCID 58406099HCID 58406099, compoundYield 14.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

2-Fluoropyridine-3-boronic acid (63.9 mg), tetrakis(triphenylphosphine)palladium (26.2 mg) and a 1 N sodium carbonate solution (453 μl) were added to a solution of (±)-N,N-di(tert-butyloxycarbonyl)-[(4aR*,6R*,8aS*)-8a-(5-bromo-2-fluorophenyl)-6-trifluoromethyl-4,4a,5,6,8,8a-hexahydro-7-oxa-3-thia-1-azanaphthalen-2-yl]amine (138 mg) in DMF (9.9 ml), and the mixture was stirred in a nitrogen atmosphere at 85° C. for seven hours. The reaction solution was cooled to room temperature and then diluted with ethyl acetate. The organic layer was washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. Dichloromethane (4.0 ml) and TFA (1.0 ml) were added to the residue, and the mixture was stirred at room temperature for four hours. When the reaction was completed, the reaction solution was diluted with dichloromethane and ice was added, followed by neutralization with a sodium bicarbonate solution. The aqueous layer was extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by NH-silica gel column chromatography. The resulting white solid was washed with diethyl ether to obtain the title compound (14.0 mg).

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. washThe organic layer was washed with water and brine
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. additionDichloromethane (4.0 ml) and TFA (1.0 ml) were added to the residue
  6. stirringthe mixture was stirred at room temperature for four hours
  7. additionthe reaction solution was diluted with dichloromethane and ice
  8. additionwas added
  9. extractionThe aqueous layer was extracted with chloroform
  10. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  11. customThe solvent was evaporated under reduced pressure
  12. customthe residue was purified by NH-silica gel column chromatography
  13. washThe resulting white solid was washed with diethyl ether

Sources & evidence

ORD record
ord-2956240d483246ab975334f28c298147
Source dataset
uspto-grants-2012_06
Patent number
US08198269B2

Reaction notes

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