Cesium fluoride → Methyl 4-[4-methoxy-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]pyridine-2-carboxylate

HRID 873514Notes

Reaction equation

HRID 873514 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][C:4]=1[CH:12]1[C:25]2[C:24](=[O:26])[CH2:23][C:22]([CH3:28])([CH3:27])[CH2:21][C:20]=2[O:19][C:18]2[CH2:17][C:16]([CH3:30])([CH3:29])[CH2:15][C:14](=[O:31])[C:13]1=2.Cl[C:33]1[CH:38]=[CH:37][N:36]=[C:35]([C:39]([O:41][CH3:42])=[O:40])[CH:34]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[F-].[Cs+]>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCCCCC.O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:33]2[CH:38]=[CH:37][N:36]=[C:35]([C:39]([O:41][CH3:42])=[O:40])[CH:34]=2)=[CH:5][C:4]=1[CH:12]1[C:25]2[C:24](=[O:26])[CH2:23][C:22]([CH3:28])([CH3:27])[CH2:21][C:20]=2[O:19][C:18]2[CH2:17][C:16]([CH3:30])([CH3:29])[CH2:15][C:14](=[O:31])[C:13]1=2

Participants

9

Reactant 4

HCID 25953Cesium fluorideHCID 80271Tri-o-tolylphosphineHCID 820890Methyl 4-ChloropicolinateHCID 131732562[4-Methoxy-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]boronic acid

Product 1

HCID 117700520Methyl 4-[4-methoxy-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]pyridine-2-carboxylateYield 20%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8058HexaneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of the [4-methoxy-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]boronic acid produced in Example 1-1 (511 mg, 1.20 mmol), methyl 4-chloropyridine-2-carboxylate (207 mg, 1.20 mmol), tri(o-tolyl)phosphine (73.3 mg, 0.24 mmol), cesium fluoride (548 mg, 3.61 mmol), and palladium(II) acetate (13.5 mg, 0.06 mol) in 1,2-dimethoxyethane (10.2 ml) was prepared at room temperature, and the suspension thus prepared was then stirred at 90° C. for 7 hours. After air-cooling, water was added to the reaction solution, and the mixed solution was then extracted with ethyl acetate. The organic layer thus obtained was dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure, and the residue thus obtained was then purified by silica gel column chromatography (ethyl acetate:hexane=34:66 to 25:75, v/v) to obtain the title compound (123 mg, yield: 20%).

Workup

  1. customwas prepared at room temperature
  2. customthe suspension thus prepared
  3. temperatureAfter air-cooling
  4. extractionthe mixed solution was then extracted with ethyl acetate
  5. customThe organic layer thus obtained
  6. dry with materialwas dried over anhydrous sodium sulfate
  7. distillationThe solvent was distilled away under reduced pressure
  8. customthe residue thus obtained
  9. customwas then purified by silica gel column chromatography (ethyl acetate

Sources & evidence

ORD record
ord-9038c0b55a3448938cc07545abdf1f64
Source dataset
uspto-grants-2015_03
Patent number
US08975263B2

Reaction notes

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