Sodium Carbonate → HCID 57475668, compound

HRID 218008Notes

Reaction equation

HRID 218008 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:44]3[CH:49]=[C:48](Br)[CH:47]=[CH:46][C:45]=3[F:51])([CH2:35][O:36][C@@H:37]([CH2:42][F:43])[CH2:38]2)[N:33]=1)C(OC(C)(C)C)=O)=O)(C)(C)C>CN(C=O)C.O.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:51][C:45]1[CH:46]=[CH:47][C:48]([C:7]2[C:2]([F:1])=[N:3][CH:4]=[CH:5][CH:6]=2)=[CH:49][C:44]=1[C@@:34]12[N:33]=[C:32]([NH2:24])[S:41][CH2:40][C@@H:39]1[CH2:38][C@H:37]([CH2:42][F:43])[O:36][CH2:35]2

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 58405992HCID 58405992, compound

Product 1

HCID 57475668HCID 57475668, compoundYield 91.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

2-Fluoropyridine-3-boronic acid (51.1 mg), tetrakis(triphenylphosphine)palladium (19.1 mg) and a 1 N sodium carbonate solution (363 μl ) were added to a solution of N,N-di(tert-butyloxycarbonyl)-[(4aR,6R,8aS)-8a-(5-bromo-2-fluorophenyl)-6-fluoromethyl-4,4a,5,6,8,8a-hexahydro-7-oxa-3-thia-1-azanaphthalen-2-yl]amine (95 mg) in DMF (6.79 ml). After replacement with nitrogen, the mixture was stirred at 85° C. for two hours. After cooling to room temperature, the mixture was diluted with water. The aqueous layer was extracted with ethyl acetate, and the organic layer was washed with water. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography. The resulting intermediate was dissolved in dichloromethane (4.0 ml). TFA (1.0 ml) was added and the mixture was stirred at room temperature for three hours. Ice was added to the reaction mixture, 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 silica gel column chromatography to obtain the title compound (59.0 mg).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washthe organic layer was washed with water
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography
  7. dissolutionThe resulting intermediate was dissolved in dichloromethane (4.0 ml)
  8. additionTFA (1.0 ml) was added
  9. stirringthe mixture was stirred at room temperature for three hours
  10. additionIce was added to the reaction mixture
  11. extractionThe aqueous layer was extracted with chloroform
  12. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  13. customThe solvent was evaporated under reduced pressure
  14. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-5050269d90084e48b1888076ee39c018
Source dataset
uspto-grants-2012_06
Patent number
US08198269B2

Reaction notes

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