HCID 54687146, compound → HCID 54704003, compound

HRID 1642035Notes

Reaction equation

HRID 1642035 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]>[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

3

Reactant 1

HCID 54687146HCID 54687146, compound

Product 1

HCID 54704003HCID 54704003, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

7-iodosancycline, 150 mg (0.28 mM), Pd(OAc)2 and 10 mL of Me0H 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 Me0H 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 before extraction into 50:25:25 water:butanol:ethyl acetate and dried in vacuo. This solid was dissolved in Me0H and the HCl salt made by bubbling in HCl gas. The solvent was removed to produce the product, substantially free of positional isomers, 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 Me0H that
  6. customwas also degassed
  7. filtrationThe solution was filtered
  8. customdried

Sources & evidence

ORD record
ord-824fa666df3e4b4597d48a29179f9399
Source dataset
uspto-grants-2012_02
Patent number
US08119622B2

Reaction notes

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