Potassium Carbonate → HCID 11466418, compound

HRID 2252420Notes

Reaction equation

HRID 2252420 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][C:10]([C@@H:13]2[C@@H:16]([CH2:17][CH2:18][C@@H:19]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[OH:20])[C:15](=[O:28])[N:14]2[C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)=[CH:9][CH:8]=1)(=O)=O.[C:38]([C:41]1[CH:42]=[C:43](B(O)O)[CH:44]=[CH:45][CH:46]=1)([OH:40])=[O:39].C(=O)([O-])[O-].[K+].[K+].S(=O)(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.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.O.ClCCl.C(O)C>[F:35][C:32]1[CH:31]=[CH:30][C:29]([N:14]2[C:15](=[O:28])[C@H:16]([CH2:17][CH2:18][C@@H:19]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[OH:20])[C@H:13]2[C:10]2[CH:11]=[CH:12][C:7]([C:45]3[CH:44]=[CH:43][CH:42]=[C:41]([C:38]([OH:40])=[O:39])[CH:46]=3)=[CH:8][CH:9]=2)=[CH:34][CH:33]=1

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 516919Sodium BisulfateHCID 27339573-Carboxyphenylboronic acidHCID 11398616HCID 11398616, compound

Product 1

HCID 11466418HCID 11466418, compoundYield 86.8%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

4-{(2S,3R)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxoazetidin-2-yl}phenyl trifluoromethanesulfonate (51.1 mg, 0.094 mmol) and 3-carboxyphenylboronic acid (21.9 mg, 0.132 mmol) were dissolved in 1:1 toluene:ethanol (2 mL). 2.0 M aqueous potassium carbonate (0.14 mL) was added and the solution degassed. Tetrakis(triphenylphosphine)palladium(0) (5.1 mg, 0.005 mmol) was added and the reaction stirred vigorously for 2 h at refluxing temperature under a nitrogen atmosphere. The cooled reaction was diluted into dichloromethane (15 mL), water (3 mL) was added and the pH was adjusted to 3 with 5% aqueous sodium bisulfate. The layers were separated and the aqueous layer extracted with dichloromethane (2×5 mL). The combined organic extracts were dried over sodium sulfate, filtered, concentrated and purified by chromatography (12 g silica gel, 5% methanol in dichloromethane) to afford 4′-{(2S,3R)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxoazetidin-2-yl]biphenyl-3-carboxylic acid (41.9 mg, 86% yield) as a colorless foam; Rf 0.15 (5% methanol in dichloromethane); 1H NMR (300 MHz, CDCl3) δ?8.31 (m, 1H), 8.09 (dt, J=7.8, 1.5 Hz, 1H), 7.79-7.39 (m, 6H), 7.23-7.32 (m, 4H), 6.90-7.02 (m, 4H), 4.75 (t, J=5.7 Hz, 1H), 4.69 (d, J=2.1 Hz), 3.12 (m, 1H), 2.10-1.90 (m, 4H) ppm; MS [M−H] 512.5. In the same manner was obtained:

Workup

  1. customthe solution degassed
  2. temperatureat refluxing temperature under a nitrogen atmosphere
  3. customThe cooled reaction
  4. additionwas added
  5. customThe layers were separated
  6. extractionthe aqueous layer extracted with dichloromethane (2×5 mL)
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by chromatography (12 g silica gel, 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-acaacf531bce4e7fb8bbebb07c2f87fe
Source dataset
uspto-grants-2008_01
Patent number
US07320972B2

Reaction notes

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