Cesium fluoride → HCID 178436313, compound

HRID 452996Notes

Reaction equation

HRID 452996 reaction equation
Br[C:2]1[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][C:3]=1[C:4](/[N:6]=[C:7]1/[N:8]([CH2:17][C@H:18]2[CH2:22][CH2:21][CH2:20][O:19]2)[N:9]([CH3:16])[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:11]/1)=[O:5].[CH:31](B(OCCCC)OCCCC)=[CH2:32].[F-].[Cs+]>CO.COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:12]([C:10]1[N:9]([CH3:16])[N:8]([CH2:17][C@H:18]2[CH2:22][CH2:21][CH2:20][O:19]2)/[C:7](=[N:6]/[C:4](=[O:5])[C:3]2[CH:23]=[C:24]([C:27]([F:30])([F:29])[F:28])[CH:25]=[CH:26][C:2]=2[CH:31]=[CH2:32])/[CH:11]=1)([CH3:15])([CH3:14])[CH3:13]

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 236543Dibutyl Vinylboronate (stabilized with Phenothiazine)HCID 178480265HCID 178480265, compound

Product 1

HCID 178436313HCID 178436313, compoundYield 86%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 887MethanolSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
130 °C

Procedure

To the mixture of Example 88, tetrakis(triphenylphosphine)palladium (0.231 g, 0.200 mmol), dibutyl vinylboronate (0.863 ml, 4.00 mmol) and cesium fluoride (1.82 g, 12.0 mmol) in MeOH (1 mL) and DME (2 mL) was added tetrakis(triphenylphosphine)palladium (0.231 g, 0.200 mmol). The mixture was heated in a sealed tube at 130° C. for 20 min. After cooling to ambient temperature, the solvent was removed under reduced pressure and the residue was diluted with EtOAc and water. The organic layer was washed with saturated aqueous NaHCO3 and brine and then concentrated. Purification by column chromatography (silica gel, 5-30% gradient of 9:1 MeOH/Et3N in EtOAC) provided the title compound 1.5 g (86% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.39 (s, 9H) 1.62-1.95 (m, 4H) 3.59-3.68 (m, 1H) 3.70-3.81 (m, J=7.14, 7.14 Hz, 1H) 3.90 (s, 3H) 4.11-4.22 (m, J=6.15, 4.16 Hz, 1H) 4.26-4.46 (m, 2H) 5.31 (d, J=12.29 Hz, 1H) 5.76 (d, J=17.85 Hz, 1H) 6.85 (s, 1H) 7.54-7.68 (m, 2H) 7.76 (d, J=8.33 Hz, 1H) 8.04 (d, J=1.59 Hz, 1H); MS (ESI) m/z 436 (M+H)+, 434 (M−H)−.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. customthe solvent was removed under reduced pressure
  3. additionthe residue was diluted with EtOAc and water
  4. washThe organic layer was washed with saturated aqueous NaHCO3 and brine
  5. concentrationconcentrated
  6. customPurification by column chromatography (silica gel, 5-30% gradient of 9:1 MeOH/Et3N in EtOAC)

Sources & evidence

ORD record
ord-af31384109274512bf31831102edc72a
Source dataset
uspto-grants-2013_07
Patent number
US08492371B2

Reaction notes

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