4-Fluorophenylboronic acid → 2-Amino-6-(4-fluoro-phenyl)-benzo[b]thiophene-3-carboxylic acid ethyl ester

HRID 1594231Notes

Reaction equation

HRID 1594231 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]2[CH:15]=[CH:14][C:13](Br)=[CH:12][C:8]=2[S:9][C:10]=1[NH2:11])=[O:5])[CH3:2].[F:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1.C([O-])(O)=O.[Na+]>O1CCOCC1.O.[Cl-].[Na+].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>[CH2:1]([O:3][C:4]([C:6]1[C:7]2[CH:15]=[CH:14][C:13]([C:21]3[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=3)=[CH:12][C:8]=2[S:9][C:10]=1[NH2:11])=[O:5])[CH3:2]

Participants

7

Reactant 3

HCID 2856454-Fluorophenylboronic acidHCID 516892Sodium BicarbonateHCID 18422163Ethyl 6-bromo-2-aminobenzo[b]thiophene-3-carboxylate

Product 1

HCID 693379972-Amino-6-(4-fluoro-phenyl)-benzo[b]thiophene-3-carboxylic acid ethyl esterYield 90%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)SolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 1d (200 mg, 0.67 mmol) in 1,4-dioxane/water (40 mL, 3:1) was added 4-fluorophenylboronic acid (209 mg, 1.34 mmol), NaHCO3 (225 mg, 2.68 mmol) and Pd(PPh3)4 (9% Pd, 79 mg, 0.067 mmol). The resultant mixture was heated at 110° C. for 1 h, diluted with brine solution (50 mL) and extracted with ethyl acetate (50 mL, 3×). The combined organic phases were dried over MgSO4, filtered, and concentrated. Flash chromatography (hexanes/ethyl acetate, 4:1) then provided the title compound (190 mg, 90%) as a pink sticky oil: MS (ES) m/z 316 (M+H)+; 1H NMR (400 MHz, CDCl3) δ8.16 (d, J=8.4 Hz, 1H), 7.69 (s, 1H), 7.62 (m, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.15 (m, 2H), 6.58 (brs, 2H), 4.46 (q, J=7.2 Hz, 2H), 1.50 (t, J=7.2 Hz, 3H).

Workup

  1. extractionextracted with ethyl acetate (50 mL, 3×)
  2. dry with materialThe combined organic phases were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-ffcbb16a549b4e8997bab2e6593a66ef
Source dataset
uspto-grants-2007_11
Patent number
US07300952B2

Reaction notes

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