Lithium Hydroxide → HCID 18506878, compound

HRID 1355434Notes

Reaction equation

HRID 1355434 reaction equation
Br[C:2]1[S:6][C:5]([N:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=2)C(=O)C)=[N:4][CH:3]=1.[C:17]1([CH3:26])[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[Li+].[OH-]>O1CCOCC1>[N:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[NH:7][C:5]1[S:6][C:2]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[CH3:26])=[CH:3][N:4]=1

Participants

6

Reactant 4

HCID 3939Lithium HydroxideHCID 62657Potassium Phosphate, TribasicHCID 27332672-Methylphenyl boronic acidHCID 18506782N-(5-Bromo-thiazol-2-yl)-N-pyridin-2-yl-acetamide

Product 1

HCID 18506878HCID 18506878, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a flame dried round bottom flask previously flushed with argon was added N-(5-bromo-thiazol-2-yl)-N-pyridin-2-yl-acetamide (5-5) (50 mg, 1.7 mmol, o-tolylboronic acid (2.6 mmol), potassium phosphate tribasic (108 mg, 5.1 mmol), palladium tetrakistriphenyl phosphine (20 mg, 0.2 mmol), and 3 mL of anhydrous dioxane. The vessel was flushed twice with argon and was heated to 100° C. under Argon. After 20 h workup was performed as follows: The reaction was cooled to ambient temperature and the dioxane was removed via rotary evaporation. The crude mixture was diluted in 1.5 mL CH2Cl2 and 2 mL water, and the resulting biphasic mixture was transferred to a Whatman 12 mL 1PS filter tube. The layers were mixed and the organic layer was drained into a collection tube; the extraction was repeated with an additional 2 mL of CH2Cl2. The organic layer was concentrated and the resulting solid was dissolved in DMSO. Purification was performed via Gilson reverse phase automated column chromatography. Only pure desired fractions were combined into a reaction vessel, contaminated fractions were discarded. An equal portion of methanol was added corresponding to the volume of acetonitrile/water present in the combined samples. LiOH monohydrate (5.0 eq.) was added to the stirred solution. The reaction was complete via MS within 10 min or less after the addition of the LiOH. The reaction was concentrated to almost complete dryness. The product was obtained as a precipitate which was filtered, washed with water, and dried. 1H NMR (CDCl3): δ8.38 (d, 1H, J=4.2 Hz), 7.68 (t, 1H, J=7.5 Hz), 7.42 (d, 1H, J=9.7 Hz), 7.33 (s, 1H), 7.27-7.31 (m, 3H), 7.08 (d, 1H, J=8.2 Hz), 6.97 (t, 1H, J=4.9 Hz), 2.46 (s, 3H). Mp: 155-160° C. MS [M+H]+=268.0.

Workup

  1. customTo a flame dried round bottom flask
  2. custompreviously flushed with argon
  3. customThe vessel was flushed twice with argon
  4. temperatureThe reaction was cooled to ambient temperature
  5. customthe dioxane was removed via rotary evaporation
  6. additionThe crude mixture was diluted in 1.5 mL CH2Cl2
  7. filtrationfilter tube
  8. additionThe layers were mixed
  9. customthe organic layer was drained into a collection tube
  10. extractionthe extraction
  11. concentrationThe organic layer was concentrated
  12. dissolutionthe resulting solid was dissolved in DMSO
  13. customPurification
  14. customOnly pure desired fractions were combined into a reaction vessel
  15. additionAn equal portion of methanol was added corresponding to the volume of acetonitrile/water
  16. waitThe reaction was complete via MS within 10 min or less
  17. concentrationThe reaction was concentrated to almost complete dryness
  18. customThe product was obtained as a precipitate which
  19. filtrationwas filtered
  20. washwashed with water
  21. customdried

Sources & evidence

ORD record
ord-f8408d44fc6f4cea9dea90553c578ea3
Source dataset
uspto-grants-2003_07
Patent number
US06586423B2

Reaction notes

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