Sodium Carbonate → HCID 86271203, compound

HRID 528002Notes

Reaction equation

HRID 528002 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][CH3:19])=[C:6]([C:8]2[C:9]3[CH:16]=[C:15](I)[NH:14][C:10]=3[N:11]=[CH:12][N:13]=2)[CH:7]=1.[F:20][C:21]1([F:36])[CH2:26][CH2:25][C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][CH2:22]1.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.C(O)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:20][C:21]1([F:36])[CH2:26][CH2:25][C:24]([C:15]2[NH:14][C:10]3[N:11]=[CH:12][N:13]=[C:8]([C:6]4[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=4[O:18][CH3:19])[C:9]=3[CH:16]=2)=[CH:23][CH2:22]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 593513932-(4,4-Difluorocyclohex-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 90418660HCID 90418660, compound

Product 1

HCID 86271203HCID 86271203, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 86587095Dimethoxyethane ethanol waterSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of Example 61A (129 mg, 0.528 mmol), 2-(4,4-difluorocyclohex-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (129 mg, 0.528 mmol), and bis(triphenylphosphine)palladium(II) dichloride (28.5 mg, 0.041 mmol) in 10 mL dimethoxyethane/ethanol/water (7/2/3) was added sodium carbonate (129 mg, 1.219 mmol). The reaction was stirred at 100° C. for 2 hours, cooled and then extracted with ethyl acetate. The organic fraction was washed with saturated sodium bicarbonate, water and brine, then dried over magnesium sulfate and concentrated. The crude material was triturated with ethyl acetate, and the solid was collected by filtration. The solid was purified via flash chromatography: Analogix Intelliflash™ 280, 24 g silica column, 20% to 60% ethyl acetate/hexanes gradient over 30 minutes to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ 12.27 (s, 1H) 8.65-8.90 (m, 1H) 7.09-7.48 (m, 3H) 6.45 (s, 1H) 6.37 (s, 1H) 3.73-3.82 (m, 3H) 2.80 (t, J=14.19 Hz, 2H) 2.69 (t, J=5.95 Hz, 2H) 2.08-2.27 (m, 2H). MS (ESI+) m/z 360.2 (M+H)+.

Workup

  1. temperaturecooled
  2. extractionextracted with ethyl acetate
  3. washThe organic fraction was washed with saturated sodium bicarbonate, water and brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe crude material was triturated with ethyl acetate
  7. filtrationthe solid was collected by filtration
  8. customThe solid was purified via flash chromatography
  9. waitAnalogix Intelliflash™ 280, 24 g silica column, 20% to 60% ethyl acetate/hexanes gradient over 30 minutes

Sources & evidence

ORD record
ord-57051830b0444c3fa5ef030a6de91a33
Source dataset
uspto-grants-2016_05
Patent number
US09346813B2

Reaction notes

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