Toluene → HCID 59118193, compound

HRID 432109Notes

Reaction equation

HRID 432109 reaction equation
C([N:8]([CH2:16][C@H:17]1[CH2:26][CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[C:22]([C:27]3[CH:36]=[CH:35][C:30]([C:31]([O:33][CH3:34])=[O:32])=[C:29](OS(C(F)(F)F)(=O)=O)[CH:28]=3)[CH:23]=2)[O:18]1)C(OC(C)(C)C)=O)C1C=CC=CC=1.[CH3:45][C:46]1[CH:51]=[CH:50][C:49](B(O)O)=[CH:48][CH:47]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:61]1([CH3:67])[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1>O.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[CH2:45]([NH:8][CH2:16][C@H:17]1[CH2:26][CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[C:22]([C:27]3[CH:28]=[C:29]([C:64]4[CH:65]=[CH:66][C:61]([CH3:67])=[CH:62][CH:63]=4)[C:30]([C:31]([O:33][CH3:34])=[O:32])=[CH:35][CH:36]=3)[CH:23]=2)[O:18]1)[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 79799Tolylboronic acidHCID 59118201HCID 59118201, compound

Product 1

HCID 59118193HCID 59118193, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a degassed solution of the compound of Example 203 (0.31 g, 0.49 mmol, 1.0 eq.) in toluene (1.0 mL) was added 4-methylphenylboronic acid (0.10 g, 0.73 mmol, 1.5 eq.), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.028 g, 0.034 mmol, 0.07 eq.) and 2M sodium carbonate (2.4 mL, 4.88 mmol, 10.0 eq.) under argon atmosphere at room temperature. The reaction mixture was allowed to heat up at 80° C. under argon atmosphere for 18 hours. The mixture was diluted with distilled water (3 mL) and extracted with diethyl ether (3×2 mL). The combined extracts were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was then treated with 4N hydrochloric acid (1.0 mL) in tetrahydrofuran (3 ml) and stirred at room temperature for 48 hours. The mixture was concentrated under reduced pressure to give white solid. Purification by HPLC followed yielded the desired product as clear oil (0.18 g, 77%). LC-MS: 578.0 (MH+), retention time: 4.63 min.

Workup

  1. extractionextracted with diethyl ether (3×2 mL)
  2. dry with materialThe combined extracts were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. additionThe resulting residue was then treated with 4N hydrochloric acid (1.0 mL) in tetrahydrofuran (3 ml)
  6. concentrationThe mixture was concentrated under reduced pressure
  7. customto give white solid
  8. customPurification by HPLC

Sources & evidence

ORD record
ord-f7d5fd7a7d354087b34e32f5ba6f3c14
Source dataset
uspto-grants-2003_12
Patent number
US06660752B2

Reaction notes

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