Sodium Carbonate → HCID 67183854, compound

HRID 1020020Notes

Reaction equation

HRID 1020020 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6](B(O)O)[CH:7]=1.Cl[C:14]1[N:19]=[CH:18][N:17]=[C:16]([NH:20][C:21]([CH:23]2[CH2:28][CH2:27][CH2:26][N:25]([C:29]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[O:30])[CH2:24]2)=[O:22])[CH:15]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:32]([O:31][C:29]([N:25]1[CH2:26][CH2:27][CH2:28][CH:23]([C:21](=[O:22])[NH:20][C:16]2[CH:15]=[C:14]([C:6]3[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=3[O:11][CH3:12])[N:19]=[CH:18][N:17]=2)[CH2:24]1)=[O:30])[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27826735-Fluoro-2-methoxyphenylboronic acidHCID 86645892HCID 86645892, compound

Product 1

HCID 67183854HCID 67183854, compoundYield 66.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-fluoro-2-methoxyphenyl boronic acid (0.20 g, 1.1 mmol) in a mixture of THF and water (6 ml, 1:1), benzyl 3-(6-chloropyrimidin-4-ylcarbamoyl)piperidine-1-carboxylate (0.35 g, 1.0 mmol) was added at 0° C. followed by palladium acetate (12 mg, 0.054 mmol), PPh3 (31 mg, 0.12 mmol) and saturated solution of sodium carbonate (2 ml). The reaction mixture was stirred at room temperature for 30 h and then filtered through a celite bed which was washed with ethyl acetate. The aqueous layer was extracted with ethyl acetate, the organic layers were combined, washed with brine, dried and evaporated under reduced pressure. The crude product was purified by column chromatography, using hexane/ethyl acetate (4:1) as eluent, to provide 0.31 g (yield: 53.8%) of 3-[6-(5-fluoro-2-methoxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester

Workup

  1. additionwas added at 0° C.
  2. filtrationfiltered through a celite bed which
  3. washwas washed with ethyl acetate
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washwashed with brine
  6. customdried
  7. customevaporated under reduced pressure
  8. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-fe7bd06d63354163b74e16e5b509033c
Source dataset
uspto-grants-2014_05
Patent number
US08716296B2

Reaction notes

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