Potassium Acetate → 3-(Acetoxymethyl)-2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)pyridin-4-ylboronic Acid

HRID 407653Notes

Reaction equation

HRID 407653 reaction equation
[C:1]([O:4][CH2:5][C:6]1[C:7]([N:13]2[N:22]=[CH:21][C:20]3[C:15](=[C:16]([F:27])[CH:17]=[C:18]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH:19]=3)[C:14]2=[O:28])=[N:8][CH:9]=[CH:10][C:11]=1Cl)(=[O:3])[CH3:2].[B:29]1(B2OC(C)(C)C(C)(C)O2)[O:33]C(C)(C)C(C)(C)[O:30]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])(=O)C.[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[C:1]([O:4][CH2:5][C:6]1[C:7]([N:13]2[N:22]=[CH:21][C:20]3[C:15](=[C:16]([F:27])[CH:17]=[C:18]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH:19]=3)[C:14]2=[O:28])=[N:8][CH:9]=[CH:10][C:11]=1[B:29]([OH:33])[OH:30])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86683941(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloropyridin-3-yl)methyl Acetate

Product 1

HCID 866839433-(Acetoxymethyl)-2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)pyridin-4-ylboronic AcidYield 96.8%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 116b (1.0 g, 2.5 mmol), Pin2B2 (3.2 g, 12.5 mmol), Pd(dppf)Cl2 (75 mg, 0.125 mmol), X-phos (75 mg, 0.25 mmol), potassium acetate (750 mg, 7.5 mmol), and dioxane (60 mL). After three cycles of vacuum/argon flush, the mixture was heated at 65° C. for 15 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was washed with 3:1 petroleum ether/ethyl acetate (10 mL) to afford 116c as yellow solid (1.0 g, LCMS purity: 75%). MS: [M+H]+ 414.2.

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. washthe resulting residue was washed with 3:1 petroleum ether/ethyl acetate (10 mL)

Sources & evidence

ORD record
ord-011552214ef84000b0be1ee67a4beb64
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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