Sodium Chloride → HCID 86651770, compound

HRID 241253Notes

Reaction equation

HRID 241253 reaction equation
[C:1]([O:5][C:6](=[O:41])[CH2:7][N:8]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH:22]([CH2:33][C:34]2[CH:39]=[CH:38][C:37](Br)=[CH:36][CH:35]=2)[NH:23][S:24]([C:27]2[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=2)(=[O:26])=[O:25])[N:17]=1)[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])([CH3:4])([CH3:3])[CH3:2].[F:42][C:43]1[CH:48]=[CH:47][C:46](B(O)O)=[CH:45][CH:44]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[Cl-].[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[C:1]([O:5][C:6](=[O:41])[CH2:7][N:8]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH:22]([CH2:33][C:34]2[CH:39]=[CH:38][C:37]([C:46]3[CH:47]=[CH:48][C:43]([F:42])=[CH:44][CH:45]=3)=[CH:36][CH:35]=2)[NH:23][S:24]([C:27]2[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=2)(=[O:26])=[O:25])[N:17]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 5

HCID 5234Sodium ChlorideHCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2856454-Fluorophenylboronic acidHCID 86651771HCID 86651771, compound

Product 1

HCID 86651770HCID 86651770, compoundYield 94.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
100 °C

Procedure

To a solution of tert-butyl({6-[(4-bromobenzyl)(pyridin-3-ylsulfonyl)aminomethyl]pyridin-2-yl}tert-butoxycarbonylamino)acetate (185 mg, 0.285 mmol) obtained in Example 9-(a) in toluene (2 ml) were added 4-fluorophenylboronic acid (61.3 mg, 0.438 mmol), palladium acetate (4.9 mg, 0.044 mmol), tripotassium phosphate (202 mg, 0.953 mmol) and water (0.2 ml), followed by being subjected to argon atmosphere. Then a solution of tricyclohexylphosphine in 20% toluene (130 μl, 0.088 mmol) was added to the mixture, and it was stirred at 100° C. for 2.5 hours under argon atmosphere. After completion of the reaction, a saturated aqueous sodium chloride solution was added to the reaction solution, followed by extraction with ethyl acetate. The separated organic layer was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography (eluent; hexane:ethyl acetate=9:1→7:3 (V/V)), and fractions containing the desired compound were concentrated under reduced pressure to afford the title compound (178 mg) as a white foam. (Yield: 94%)

Workup

  1. customAfter completion of the reaction
  2. extractionfollowed by extraction with ethyl acetate
  3. dry with materialThe separated organic layer was dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. additioncontaining the desired compound
  6. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-bd68a478ee604b3fa8d845d324da98c7
Source dataset
uspto-grants-2014_02
Patent number
US08648097B2

Reaction notes

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