Acetonitrile → HCID 118511153, compound

HRID 1478181Notes

Reaction equation

HRID 1478181 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH2:18][CH2:17][C:12]3([O:16][CH2:15][CH2:14][O:13]3)[CH2:11][CH:10]=2)O1.N[C:21]1[C:22](=[O:34])N(C2CCCCC2)[N:24](C)[C:25]=1C.[C:35]([O-:38])([O-])=[O:36].[K+].[K+].[CH2:41](Cl)Cl.[C:44](#N)[CH3:45]>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].O>[CH3:41][C:21]1[C:25]([C:35]([O:38][CH2:44][CH3:45])=[O:36])=[N:24][O:34][C:22]=1[C:9]1[CH2:18][CH2:17][C:12]2([O:13][CH2:14][CH2:15][O:16]2)[CH2:11][CH:10]=1

Participants

8

Reactant 5

HCID 6342AcetonitrileHCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 36970768-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4-dioxaspiro(4.5)dec-7-eneHCID 612730214-amino-2-cyclohexyl-1,5-dimethyl-2,3-dihydro-1H-pyrazol-3-one2×

Product 1

HCID 118511153HCID 118511153, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a 2-5 mL microwave vial containing a solution of 4,4,5,5-tetramethyl-2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1,3,2-dioxaborolane (586 mg, 2.200 mmol) in acetonitrile (2 mL) was added ethyl 5-bromo-4-methylisoxazole-3-carboxylate (Intermediate D) (515 mg, 2.200 mmol) followed by K2CO3 (912 mg, 6.60 mmol), PdCl2(dppf).CH2Cl2 adduct (17.97 mg, 0.022 mmol), and water (0.667 mL). The vial was flushed with nitrogen and stirred in the microwave (Biotage Smith Initiator) at 80° C. for 1 hour and 100° C. for 30 minutes. The resulting mixture was partitioned between water (30 mL) and EtOAc (30 mL). The organic phase was washed with brine (30 mL), dried over MgSO4, filtered and concentrated under reduced pressure to give an orange oil. The crude material was adsorbed onto silica and purification by chromatography eluting with 0-40% EtOAc in iso-hexane afforded the title compound;

Workup

  1. customThe vial was flushed with nitrogen
  2. customThe resulting mixture was partitioned between water (30 mL) and EtOAc (30 mL)
  3. washThe organic phase was washed with brine (30 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give an orange oil
  8. customThe crude material was adsorbed onto silica and purification by chromatography
  9. washeluting with 0-40% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-85c2997541454eceaa9a42b99f2a4d17
Source dataset
uspto-grants-2016_08
Patent number
US09403810B2

Reaction notes

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