Toluene → HCID 178426007, compound

HRID 1926246Notes

Reaction equation

HRID 1926246 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]2[C:3]=1[CH:4]=[C:5]([OH:13])[N:6]=[CH:7]2.[CH3:14][Zn]C.C1(C)C=CC=CC=1.[NH4+].[Cl-]>C1COCC1.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:12][C:9]1[CH:10]=[CH:11][C:2]([CH3:14])=[C:3]2[C:8]=1[CH:7]=[N:6][C:5]([OH:13])=[CH:4]2

Participants

7

Reactant 4

HCID 1140TolueneHCID 25517Ammonium ChlorideHCID 178477796HCID 178477796, compoundHCID 1785152975-Bromo-8-fluoroisoquinolin-3-ol

Product 1

HCID 178426007HCID 178426007, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-Bromo-8-fluoroisoquinolin-3-ol (76.5 mg, 0.316 mmol), 2.0 M of dimethylzinc in toluene (0.40 mL, 0.80 mmol), and Pd(PPh3)4 (22 mg, 0.019 mmol) in THF in a microwave reactor tube was heated in the microwave reactor to 80° C. for 60 min. The reaction solution was poured into sat. aq. NH4Cl, and the resulting mixture was extracted with DCM (3×25 mL). The combined DCM extracts were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue was triturated with Et2O. The resulting light greenish-yellow solid was washed with Et2O and dried in vacuo to give the title compound as light greenish-yellow solid. It was used in the next step without further purification. MS(ES+): m/z=178.17 (100) [MH+]. HPLC: tR=2.36 min (polar—5 min, ZQ2).

Workup

  1. extractionthe resulting mixture was extracted with DCM (3×25 mL)
  2. washThe combined DCM extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was triturated with Et2O
  7. washThe resulting light greenish-yellow solid was washed with Et2O
  8. customdried in vacuo

Sources & evidence

ORD record
ord-4d246d73baf2456fa0838c85915ee609
Source dataset
uspto-grants-2012_05
Patent number
US08178668B2

Reaction notes

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