Hydrochloric Acid → 3-[5-(Trifluoroacetyl)thiophen-2-yl]benzoic Acid

HRID 874974Notes

Reaction equation

HRID 874974 reaction equation
Br[C:2]1[S:6][C:5]([C:7](=[O:12])[C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.[C:13]([C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[CH:20][CH:21]=1)([OH:15])=[O:14].C([O-])([O-])=O.[Na+].[Na+].Cl>CN(C=O)C.O.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>[F:9][C:8]([F:11])([F:10])[C:7]([C:5]1[S:6][C:2]([C:20]2[CH:21]=[C:16]([CH:17]=[CH:18][CH:19]=2)[C:13]([OH:15])=[O:14])=[CH:3][CH:4]=1)=[O:12]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 27339573-Carboxyphenylboronic acidHCID 199715871-(5-Bromothiophen-2-yl)-2,2,2-trifluoroethan-1-one

Product 1

HCID 248966243-[5-(Trifluoroacetyl)thiophen-2-yl]benzoic AcidYield 79%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

1-(5-Bromothiophen-2-yl)-2,2,2-trifluoroethanone (0.8 g, 3.09 mmol) and 3-carboxyphenylboronic acid (0.5 g, 3.01 mmol) were dissolved in DMF (10 mL) and the solution was purged with argon for 10 min. 2M aqueous solution of Na2CO3 (0.65 g, 6.17 mmol) and catalytic Pd(PPh3)4 (178 mg, 0.15 mmol) were added to the reaction mixture and heated to 90° C. for 10 h. The reaction mixture was cooled to room temperature, diluted with water and acidified to pH˜6 with 1.5 N HCl. The crude product was extracted with EtOAc. The combined extracts were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was triturated with diethyl ether to get 3-(5-(2,2,2-trifluoroacetyl)thiophen-2-yl)benzoic acid (700 mg, yield 79%). 1H NMR (400 MHz, DMSO-d6) δ 13.35 (br s, 1H), 8.31-8.30 (m, 1H), 8.16-8.11 (m, 2H), 8.04-8.02 (d, J=7.6 Hz, 1H), 7.93-7.92 (d, J=4.3 Hz, 1H), 7.67-7.63 (t, J=7.8 Hz, 1H). MS (ESI) m/z: Calculated for C13H7F3O3S: 300.01. found: 299.0 (M−H)−

Workup

  1. customthe solution was purged with argon for 10 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionThe crude product was extracted with EtOAc
  4. dry with materialThe combined extracts were dried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was triturated with diethyl ether

Sources & evidence

ORD record
ord-6f22cc54602345b5b2c1deb08e0b890f
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Reaction notes

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