Potassium Carbonate → HCID 86600750, compound

HRID 2252453Notes

Reaction equation

HRID 2252453 reaction equation
[Si:1]([O:8][C@H:9]([C:46]1[CH:51]=[CH:50][C:49]([F:52])=[CH:48][CH:47]=1)[CH2:10][CH2:11][C@@H:12]1[C@@H:15]([C:16]2[CH:21]=[CH:20][C:19](B3OC(C)(C)C(C)(C)O3)=[CH:18][C:17]=2[O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33])[N:14]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:13]1=[O:45])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[C:53]([O:56][C@@H:57]1[C@@H:62]([O:63][C:64](=[O:66])[CH3:65])[C@H:61]([O:67][C:68](=[O:70])[CH3:69])[C@@H:60]([CH2:71][O:72][C:73](=[O:75])[CH3:74])[O:59][C@H:58]1[C:76]1[CH:81]=[CH:80][CH:79]=[C:78](Br)[CH:77]=1)(=[O:55])[CH3:54].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.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:53]([O:56][C@@H:57]1[C@@H:62]([O:63][C:64](=[O:66])[CH3:65])[C@H:61]([O:67][C:68](=[O:70])[CH3:69])[C@@H:60]([CH2:71][O:72][C:73](=[O:75])[CH3:74])[O:59][C@H:58]1[C:76]1[CH:77]=[C:78]([C:19]2[CH:20]=[CH:21][C:16]([C@@H:15]3[C@@H:12]([CH2:11][CH2:10][C@H:9]([O:8][Si:1]([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2])[C:46]4[CH:51]=[CH:50][C:49]([F:52])=[CH:48][CH:47]=4)[C:13](=[O:45])[N:14]3[C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)=[C:17]([O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:33])[CH3:34])[CH:18]=2)[CH:79]=[CH:80][CH:81]=1)(=[O:55])[CH3:54]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 59781994(3R,4S)-3-[(3S)-3-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]-3-(4-fluorophenyl)propyl]-4-[2-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-phenyl-2-azetidinoneHCID 59842194HCID 59842194, compound

Product 1

HCID 86600750HCID 86600750, compoundYield 27%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

The resulting brown oil which is (3R,4S)-3-[(3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-3-(4-fluorophenyl)propyl]-4-[2-{[tert-butyl(dimethyl)silyl]oxy}-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-phenylazetidin-2-one was dissolved with (1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-(3-bromophenyl)-D-glucitol in 4.0 mL of toluene and 0.5 mL of ethanol. 0.150 mL of 4 N potassium carbonate was added followed by 7 mg of tetrakis(triphenylphosphine)palladium(0). The entire reaction was degassed three times with argon then heated to reflux for 1.5 h. After this time the reaction was cooled to room temperature and diluted with 25 mL of water and extracted with 1:1 hexane-ethyl acetate (3×75 mL). The organic layers were combine, dried over sodium sulfate, filtered, concentrated and purified by column chromatography (12 g silica gel, 5% to 95% ethyl acetate-hexane) to afford 41.6 mg (27%) of (1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-(3′-{[tert butyl(dimethyl)silyl]oxy}-4′-{(2S,3R)-3-[(3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-3-(4-fluorophenyl)propyl]-4-oxo-1-phenylazetidin-2-yl}biphenyl-3-yl)-D-glucitol as a clear oil.

Workup

  1. customThe entire reaction
  2. customwas degassed three times with argon
  3. temperaturethen heated
  4. temperatureto reflux for 1.5 h
  5. additiondiluted with 25 mL of water
  6. extractionextracted with 1:1 hexane-ethyl acetate (3×75 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by column chromatography (12 g silica gel, 5% to 95% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-da34065706954e04bec65329b2b53f61
Source dataset
uspto-grants-2008_01
Patent number
US07320972B2

Reaction notes

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