Trifluoroacetic acid → HCID 58405983, compound

HRID 218011Notes

Reaction equation

HRID 218011 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:42]3[S:43][CH:44]=[C:45](Br)[CH:46]=3)([CH2:35][O:36][CH2:37][CH2:38]2)[N:33]=1)C(OC(C)(C)C)=O)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(=O)(O)[O-].[Na+]>CN(C=O)C.O.ClCCl.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:1][C:2]1[C:7]([C:45]2[CH:46]=[C:42]([C@@:34]34[N:33]=[C:32]([NH2:24])[S:41][CH2:40][C@@H:39]3[CH2:38][CH2:37][O:36][CH2:35]4)[S:43][CH:44]=2)=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

10

Reactant 5

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 67217146HCID 67217146, compound

Product 1

HCID 58405983HCID 58405983, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

2-Fluoropyridine-3-boronic acid (26.9 mg), tetrakis(triphenylphosphine)palladium (11.0 mg) and a 1 N sodium carbonate solution (191 μl) were sequentially added to a solution of (±)-N,N-di-(tert-butyloxycarbonyl)-[(4aR*,8aS*)-8a-(4-bromothiophen-2-yl)-4,4a,5,6,8,8a-hexahydro-7-oxa-3-thia-1-azanaphthalen-2-yl]amine obtained in Preparation Example 19-(3) (51.0 mg) in DMF (2.0 ml). After replacement with nitrogen, the mixture was stirred at 80° C. for five hours. The reaction solution was returned to room temperature and 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 to obtain an intermediate. The resulting intermediate was dissolved in dichloromethane (5.0 ml). TFA (2.0 ml) was added and the mixture was stirred at room temperature for three hours. Ice was added to the mixture, followed by neutralization with a sodium bicarbonate solution. The aqueous layer was extracted with ethyl acetate, 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 to obtain the title compound (22.0 mg).

Workup

  1. customwas returned 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. customto obtain an intermediate
  8. stirringthe mixture was stirred at room temperature for three hours
  9. additionIce was added to the mixture
  10. extractionThe aqueous layer was extracted with ethyl acetate
  11. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  12. customThe solvent was evaporated under reduced pressure
  13. customthe residue was purified by NH-silica gel column chromatography

Sources & evidence

ORD record
ord-29c059e37e8b4616957ca73a84c85758
Source dataset
uspto-grants-2012_06
Patent number
US08198269B2

Reaction notes

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