Sodium Carbonate → HCID 136242950, compound

HRID 918903Notes

Reaction equation

HRID 918903 reaction equation
[CH2:1]([N:8]1[N:17]=[C:16](Cl)[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](B2OC(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.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[N: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

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27346502-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 24751992HCID 24751992, compound

Product 1

HCID 136242950HCID 136242950, compoundYield 7.5%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of 2-benzyl-4-chloro-2H-phthalazin-1-one (1.35 g, 5 mmol), 2-methoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenol (1.50 g, 6 mmol), Pd(PPh3)4 (0.87 g, 0.75 mmol) and Na2CO3 (2.12 g, 20 mmol) in toluene (25 mL), ethanol (12.5 mL) and water (12.5 mL) was degassed and then heated to reflux with stirring for 19 h. After that time, the reaction was cooled to rt and diluted with ethyl acetate (150 mL) and water (100 mL). The organic phase was separated, washed with water (2×30 mL) then brine (50 mL), dried over MgSO4 and concentrated under reduced pressure. The residue was triturated with hexanes (100 mL) to give a yellow solid. The product was purified by flash column chromatography (silica gel, 70:30 hexanes/ethyl acetate) followed by recrystallization from CHCl3/hexanes to give 2-benzyl-4-(4-hydroxy-3-methoxyphenyl)phthalazin-1(2H)-one (0.135 g, 7.5%) as a white solid: mp 197-200° C.; 1H NMR (400 MHz, CDCl3) δ 8.54-8.52 (m, 1H), 7.79-7.71 (m, 3H), 7.52 (d, J=7.2 Hz, 2H), 7.34-7.25 (m, 4H), 7.11-7.04 (m, 2H), 5.82 (s, 1H), 5.47 (s, 2H), 3.93 (s, 3H); ESI MS m/z 359 [M+1]+.

Workup

  1. customwas degassed
  2. temperatureheated
  3. temperatureto reflux
  4. additiondiluted with ethyl acetate (150 mL) and water (100 mL)
  5. customThe organic phase was separated
  6. washwashed with water (2×30 mL)
  7. dry with materialbrine (50 mL), dried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was triturated with hexanes (100 mL)
  10. customto give a yellow solid
  11. customThe product was purified by flash column chromatography (silica gel, 70:30 hexanes/ethyl acetate)
  12. customfollowed by recrystallization from CHCl3/hexanes

Sources & evidence

ORD record
ord-338ced91ece24f2a8bc355deefa5bfcb
Source dataset
uspto-grants-2016_03
Patent number
US09271978B2

Reaction notes

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