Potassium Acetate → 3-(Acetoxymethyl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)pyridin-4-ylboronic Acid

HRID 592980Notes

Reaction equation

HRID 592980 reaction equation
[C:1]([O:4][CH2:5][C:6]1[C:7]([N:13]2[CH2:25][CH2:24][C:23]3[N:22]4[C:17]([CH2:18][CH2:19][CH2:20][CH2:21]4)=[CH:16][C:15]=3[C:14]2=[O:26])=[N:8][CH:9]=[CH:10][C:11]=1Cl)(=[O:3])[CH3:2].[B:27]1(B2OC(C)(C)C(C)(C)O2)[O:31]C(C)(C)C(C)(C)[O:28]1.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].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.O1CCOCC1>[C:1]([O:4][CH2:5][C:6]1[C:7]([N:13]2[CH2:25][CH2:24][C:23]3[N:22]4[C:17]([CH2:18][CH2:19][CH2:20][CH2:21]4)=[CH:16][C:15]=3[C:14]2=[O:26])=[N:8][CH:9]=[CH:10][C:11]=1[B:27]([OH:31])[OH:28])(=[O:3])[CH3:2]

Participants

7

Reactant 3

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 86684463(4-Chloro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)pyridin-3-yl)methyl acetate

Product 1

HCID 866844643-(Acetoxymethyl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)pyridin-4-ylboronic AcidYield 108.7%

Reagents, catalysts & solvents 3

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 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 244b (900 mg, 2.4 mmol), Pin2B2 (3.05 g, 12 mmol), Pd(dppf)Cl2 (98 mg, 0.12 mmol), X-phos (114 mg, 0.24 mmol), potassium acetate (720 mg, 7.2 mmol), and dioxane (20 mL). After three cycles of vacuum/argon flush, the mixture was heated at 65° C. for 4 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was washed with 5:1 petroleum ether/ethyl acetate (10 mL) to afford 244c as a yellow solid (1.0 g, purity: 60%). MS-ESI: [M+H]+ 384.1.

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 5:1 petroleum ether/ethyl acetate (10 mL)

Sources & evidence

ORD record
ord-95a5c008bece41dfb4c5fad119ac415b
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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