Potassium Acetate → 3-(Acetoxymethyl)-2-(10-fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-4-ylboronic Acid

HRID 592939Notes

Reaction equation

HRID 592939 reaction equation
[C:1]([O:4][CH2:5][C:6]1[C:7]([N:13]2[CH2:26][CH2:25][N:16]3[C:17]4[CH2:18][CH2:19][CH2:20][CH2:21][C:22]=4[C:23]([F:24])=[C:15]3[C:14]2=[O:27])=[N:8][CH:9]=[CH:10][C:11]=1Cl)(=[O:3])[CH3:2].[B:28]1(B2OC(C)(C)C(C)(C)O2)[O:32]C(C)(C)C(C)(C)[O:29]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[CH2:26][CH2:25][N:16]3[C:17]4[CH2:18][CH2:19][CH2:20][CH2:21][C:22]=4[C:23]([F:24])=[C:15]3[C:14]2=[O:27])=[N:8][CH:9]=[CH:10][C:11]=1[B:28]([OH:32])[OH:29])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86684433(4-Chloro-2-(10-fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl Acetate

Product 1

HCID 866844343-(Acetoxymethyl)-2-(10-fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-4-ylboronic AcidYield 67.1%

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 231b (600 mg, 1.53 mmol), Pin2B2 (1.94 g, 7.65 mmol), PdCl2(dppf) (65 mg, 0.080 mmol), X-Phos (73 mg, 0.15 mmol), potassium acetate (304 mg, 3.1 mmol), and dioxane (30 mL). After three cycles of vacuum/argon flush, the mixture was heated at 65° C. for 5 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was washed with petroleum ether to afford 231c (412 mg, 67%) as yellow solid. MS-ESI: [M+H]+ 402.1

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 petroleum ether

Sources & evidence

ORD record
ord-943d2aec05534a8b9b98b083a8b3d028
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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