HCID 54687146, compound → HCID 54704003, compound

HRID 1161639Notes

Reaction equation

HRID 1161639 reaction equation
[CH3:1][N:2]([C@@H:4]1[C:22](=[O:23])[C:21]([C:24]([NH2:26])=[O:25])=[C:20]([OH:27])[C@:19]2([OH:28])[C@H:5]1[CH2:6][C@H:7]1[C:16]([C:17]2=[O:18])=[C:15]([OH:29])[C:14]2[C:9](=[C:10](I)[CH:11]=[CH:12][C:13]=2[OH:30])[CH2:8]1)[CH3:3]>CC([O-])=O.CC([O-])=O.[Pd+2].CO>[CH3:1][N:2]([C@@H:4]1[C:22](=[O:23])[C:21]([C:24]([NH2:26])=[O:25])=[C:20]([OH:27])[C@:19]2([OH:28])[C@H:5]1[CH2:6][C@H:7]1[C:16]([C:17]2=[O:18])=[C:15]([OH:29])[C:14]2[C:9](=[C:10]([C:4]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:5]=3)[CH:11]=[CH:12][C:13]=2[OH:30])[CH2:8]1)[CH3:3]

Participants

4

Reactant 1

HCID 54687146HCID 54687146, compound

Product 1

HCID 54704003HCID 54704003, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolvent

Procedure

7-iodosancycline, 150 mg (0.28 mM), Pd(OAc)2 and 10 mL of MeOH are added to a flask with a stir bar and the system degassed 3× using argon. Na2CO3 (87 mg, 0.8 mM) dissolved in water and argon degassed is added via syringe is added along with phenylboronic acid (68 mg, 0.55 mM) in MeOH that was also degassed. The reaction was followed by HPLC for 2 hours and cooled to room temperature. The solution was filtered, and dried to produce a crude mixture. The solid was dissolved in dimethylformamide and injected onto a preparative HPLC system using C18 reverse-phase silica. The fraction at 36-38 minutes was isolated, and the solvent removed in vacuo to yield the product plus salts. The salts were removed by extraction into 50:25:25 water, butanol, ethyl acetate and dried in vacuo. This solid was dissolved in MeOH and the HCl salt made by bubbling in HCl gas. The solvent was removed to produce the product in 42% yield as a yellow solid.

Workup

  1. customthe system degassed 3×
  2. dissolutionNa2CO3 (87 mg, 0.8 mM) dissolved in water
  3. customargon degassed
  4. additionis added via syringe
  5. additionis added along with phenylboronic acid (68 mg, 0.55 mM) in MeOH that
  6. customwas also degassed
  7. filtrationThe solution was filtered
  8. customdried

Sources & evidence

ORD record
ord-46017149a1b64d9bbdcadd29bdf4ae82
Source dataset
uspto-grants-2010_10
Patent number
US07820641B2

Reaction notes

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