Sodium Carbonate → 2-benzyl-4-(4-hydroxy-3-methoxyphenyl) isoquinolin-1(2H)-one

HRID 918908Notes

Reaction equation

HRID 918908 reaction equation
[CH2:1]([N:8]1[CH:17]=[C:16](Br)[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:20][O:21][C:22]1[CH:27]=[C:26](C2OC(C)(C)C(C)(C)O2)[CH:25]=[CH:24][C:23]=1[OH:37].C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O.C(OCC)(=O)C.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>[CH2:1]([N:8]1[CH:17]=[C:16]([C:26]2[CH:25]=[CH:24][C:23]([OH:37])=[C:22]([O:21][CH3:20])[CH:27]=2)[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 708927422-benzyl-4-bromoisoquinolin-1(2H)-oneHCID 867235822-Methoxy-4-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenol

Product 1

HCID 766837472-benzyl-4-(4-hydroxy-3-methoxyphenyl) isoquinolin-1(2H)-oneYield 45%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-benzyl-4-bromoisoquinolin-1(2H)-one (0.50 g, 1.59 mmol), 2-methoxy-4-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenol (0.477 g, 1.90 mmol) and Na2CO3 (0.843 g, 7.95 mmol) in toluene (30 mL), ethanol (30 mL) and water (5 mL) was degassed under nitrogen. Pd(PPh3)4 (0.183 g, 0.157 mmol) was added and the reaction was stirred at 90° C. for 16 h under nitrogen. After that time, the mixture was cooled to rt and diluted with ethyl acetate (250 mL). The organic phase was separated, washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure. The product was purified by flash column chromatography (silica gel, 70:30 hexanes/ethyl acetate) to give 2-benzyl-4-(4-hydroxy-3-methoxyphenyl) isoquinolin-1(2H)-one (0.253 g, 45%) as a white solid: mp 165-167° C.; 1H NMR (400 MHz, CDCl3) δ 8.56 (d, J=8.2 Hz, 1H), 7.58-7.65 (m, 1H), 7.50-7.57 (m, 2H), 7.28-7.40 (m, 5H), 7.05 (s, 1H), 6.99 (d, J=8.6 Hz, 1H), 6.84-6.89 (m, 2H), 5.70 (s, 1H), 5.27 (s, 2H), 3.89 (s, 3H); ESI MS m/z 358 [M+H]+.

Workup

  1. customwas degassed under nitrogen
  2. temperatureAfter that time, the mixture was cooled to rt
  3. customThe organic phase was separated
  4. washwashed with water and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe product was purified by flash column chromatography (silica gel, 70:30 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-466591340e3c4407bd39a87d5bb7dbf7
Source dataset
uspto-grants-2016_03
Patent number
US09271978B2

Reaction notes

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