4-(Trifluoromethyl)phenylboronic acid → HCID 58056548, compound

HRID 555670Notes

Reaction equation

HRID 555670 reaction equation
[CH3:1][O:2][C:3](=[O:26])[CH2:4][CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([Cl:15])[CH:13]=2)[N:8]([S:16]([C:19]2[CH:20]=[N:21][CH:22]=[C:23](Br)[CH:24]=2)(=[O:18])=[O:17])[CH:7]=1.[F:27][C:28]([F:39])([F:38])[C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1>O1CCOCC1.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>[CH3:1][O:2][C:3](=[O:26])[CH2:4][CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([Cl:15])[CH:13]=2)[N:8]([S:16]([C:19]2[CH:20]=[N:21][CH:22]=[C:23]([C:32]3[CH:33]=[CH:34][C:29]([C:28]([F:39])([F:38])[F:27])=[CH:30][CH:31]=3)[CH:24]=2)(=[O:18])=[O:17])[CH:7]=1

Participants

5

Reactant 2

HCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 58056470HCID 58056470, compound

Product 1

HCID 58056548HCID 58056548, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

In a micro wave test tube, 3-[1-(5-bromo pyridine-3-sulfonyl)-5-chloro-1H-indol-3-yl]propionic acid methyl ester (11, 40 mg, 0.00009 mol), 4-(trifluoromethyl)-phenylboronic acid (12, 52 mg, 0.00027 mol), and tetrakis(triphenylphosphine)palladium(0) (4 mg, 0.000003 mol) were combined in 4 mL of 1,4-dioxane. The vessel was purged with argon for 2-3 minutes, then 0.1 mL of 1N K2CO3 was added. The vessel was microwaved at 108° C. for 40 minutes. TLC (20% ethyl acetate,/hexane) indicated a new spot and total disappearance of starting material. The crude mixture was transferred to a separatory funnel and extracted with 3×40 mL of ethyl acetate and washed with water, brine, and dried over MgSO4. The solution was filtered and the filtrate roto evaporated to near dryness. Silica and 5 mL of ethyl acetate were added and the solvent removed. Chromatography was run using a gradient solvent condition of 0 to 20% ethyl acetate/hexane over 18 minutes, then 20 to 30% over 10 minutes to isolate the desired compound. 1H NMR consistent with structure.

Workup

  1. customThe vessel was purged with argon for 2-3 minutes
  2. addition0.1 mL of 1N K2CO3 was added
  3. customThe vessel was microwaved at 108° C. for 40 minutes
  4. customThe crude mixture was transferred to a separatory funnel
  5. extractionextracted with 3×40 mL of ethyl acetate
  6. washwashed with water, brine
  7. dry with materialdried over MgSO4
  8. filtrationThe solution was filtered
  9. customthe filtrate roto evaporated
  10. additionSilica and 5 mL of ethyl acetate were added
  11. customthe solvent removed
  12. customover 18 minutes

Sources & evidence

ORD record
ord-72503b9708c04b32ab34e716f3879024
Source dataset
uspto-grants-2011_11
Patent number
US08053463B2

Reaction notes

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