Ethanol → HCID 59643969, compound

HRID 2252421Notes

Reaction equation

HRID 2252421 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.[N+:38]([C:41]1[CH:42]=[C:43](B(O)O)[CH:44]=[CH:45][CH:46]=1)([O-:40])=[O:39].C(O)C.C(=O)([O-])[O-].[K+].[K+]>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.ClCCl>[F:35][C:32]1[CH:31]=[CH:30][C:29]([N:14]2[C@H:13]([C:10]3[CH:9]=[CH:8][C:7]([C:45]4[CH:44]=[CH:43][CH:42]=[C:41]([N+:38]([O-:40])=[O:39])[CH:46]=4)=[CH:12][CH:11]=3)[C@@H:16]([CH2:17][CH2:18][C@@H:19]([C:21]3[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=3)[OH:20])[C:15]2=[O:28])=[CH:34][CH:33]=1

Participants

8

Reactant 4

HCID 702EthanolHCID 16773-Nitrophenylboronic AcidHCID 11430Potassium CarbonateHCID 11398616HCID 11398616, compound

Product 1

HCID 59643969HCID 59643969, compoundYield 95.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

4-{(2S,3R)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxoazetidin-2-yl}phenyl trifluoromethanesulfonate (50.0 mg, 0.092 mmol) and 3-nitrophenylboronic acid (21.6 mg, 0.129 mmol) were dissolved in 1:1 toluene:ethanol (2 mL). 2.0 M aqueous potassium carbonate (0.092 mL) was added and the solution degassed. Tetrakis(triphenylphosphine)palladium(0) (5.7 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). The layers were separated and the aqueous layer further extracted with dichloromethane (2×5 mL). The combined extracts were dried over sodium sulfate, filtered, concentrated and purified by chromatography (12 g silica gel, 5% to 50% ethyl acetate-hexane) to afford (3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(3′-nitrobiphenyl-4-yl)azetidin-2-one (45.0 mg, 95% yield) as a clear film; Rf 0.33 (50% ethyl acetate-hexane); 1H NMR (300 MHz, CDCl3) δ ?8.42 (m, 1H), 8.21 (ddd, J=8.1, 2.4, 1.2 Hz, 1H), 7.89 (ddd, J=7.9, 1.5, 1.2 Hz, 1H), 7.63 (d, J=8.1 Hz, 2H), 7.45 (d, J=8.1 Hz, 2H), 7.33-7.22 (m, 4H), 7.04-6.92 (m, 4H), 4.76 (t, J=6.0 Hz, 1H), 4.71 (d, J=2.1 Hz, 1H), 3.14 (m, 1H), 1.91-2.11 (m, 4H) ppm; MS [M−OH] 497.5.

Workup

  1. customthe solution degassed
  2. temperatureat refluxing temperature under a nitrogen atmosphere
  3. customThe cooled reaction
  4. customThe layers were separated
  5. extractionthe aqueous layer further extracted with dichloromethane (2×5 mL)
  6. dry with materialThe combined extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by chromatography (12 g silica gel, 5% to 50% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-545fa75a9e84492cbd6e4d11247ea6b2
Source dataset
uspto-grants-2008_01
Patent number
US07320972B2

Reaction notes

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