Benzyl Alcohol → HCID 58525656, compound
Reaction equation
C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[C:43](=[O:46])([O-])[O-:44].[Na+].[Na+].Br[C:50]1[C:59]2[C:54](=[C:55]([F:60])[CH:56]=[CH:57][CH:58]=2)[C:53](=[O:61])[N:52]([CH2:62][C:63]2[O:64][CH:65]=[CH:66][N:67]=2)[C:51]=1[CH3:68].C(O)C1C=CC=CC=1.C1(C)C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:60][C:55]1[CH:56]=[CH:57][CH:58]=[C:59]2[C:54]=1[C:53](=[O:61])[N:52]([CH2:62][C:63]1[O:64][CH:65]=[CH:66][N:67]=1)[C:51]([CH3:68])=[C:50]2[C:43]([OH:44])=[O:46]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 110 °C
Procedure
A mixture of palladium acetate (21 mg, 0.095 mmol), 4,5-bis-diphenylphosphanyl-9,9-dimethyl-9H-xanthene (=Xantphos, 55 mg, 0.095 mmol), sodium carbonate (303 mg, 2.86 mmol), 4-bromo-8-fluoro-3-methyl-2-oxazol-2-ylmethyl-2H-isoquinolin-1-one (321 mg, 0.952 mmol), and benzyl alcohol (0.297 mL, 2.87 mmol) in toluene (3 mL, 30 mmol) was stirred under an atmosphere of carbon monoxide (P=3 bar) at 110° C. overnight. LC/MS indicated the formation of the title product and its benzyl ester (8-fluoro-3-methyl-2-oxazol-2-ylmethyl-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid benzyl ester) in ca. 1:1 ratio. The reaction mixture was dissolved in 5 ml of ethanol, filtered through a short plug of celite and evaporated. It was partitioned between ethyl acetate (50 ml) and 0.5M aq. NaOH (2×25 ml). The combined aqueous solution was acidified with conc. aq. HCl, extracted with ethyl acetate (40 ml), the organic phase was washed with brine, dried (MgSO4) and evaporated to give 105 mg of the title product, yield 36.5%. LC-MS (m/z) 303.3 (MH+), tR=0.57.
Sources & evidence
- ORD record
- ord-50dd64eec9da4c199a6e4a8f32450fcb
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08415373B2
Reaction notes
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