Sodium Carbonate → 5-(3-Fluoro-phenyl)-3-[isopropyl-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester

HRID 73172

Reaction equation

HRID 73172 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][CH:7]=1.[CH3:11][O:12][C:13]([C:15]1[S:16][C:17](Br)=[CH:18][C:19]=1[N:20]([CH:30]([CH3:32])[CH3:31])[C:21]([CH:23]1[CH2:28][CH2:27][CH:26]([CH3:29])[CH2:25][CH2:24]1)=[O:22])=[O:14].C1(C)C=CC=CC=1.CO.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.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>[CH3:11][O:12][C:13]([C:15]1[S:16][C:17]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)=[CH:18][C:19]=1[N:20]([CH:30]([CH3:32])[CH3:31])[C:21]([CH:23]1[CH2:24][CH2:25][CH:26]([CH3:29])[CH2:27][CH2:28]1)=[O:22])=[O:14]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 207757685-Bromo-3-[isopropyl-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl esterHCID 21867641Toluene methanol

Product 1

HCID 597523165-(3-Fluoro-phenyl)-3-[isopropyl-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl esterYield 99.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

To the mixture of 3-fluorobenzeneboronic acid (25.0 mg, 0.180 mmol) and 5-Bromo-3-[isopropyl-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (24 mg, 0.060 mmol) in 5:1 mixture of toluene/MeOH (1.0 mL) was added a solution of Pd(PPh3)4 (7.0 mg, 0.006 mmol, 10 mol %) in toluene (0.5 mL) followed by aqueous 2M Na2CO3 solution (0.06 mL, 0.120 mmol). The resultant reaction mixture was heated at 70° C. for 18 h, cooled to room temperature, filtered off through MgSO4 and washed with EtOAc. Evaporation of the solvent and purification of the residue over preparative TLC using ethyl acetate/hexane (20:80) as an eluent furnished (25.0 mg, 99% yield) of 5-(3-Fluoro-phenyl)-3-[isopropyl-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester.

Workup

  1. customThe resultant reaction mixture
  2. temperaturecooled to room temperature
  3. filtrationfiltered off through MgSO4
  4. washwashed with EtOAc
  5. customEvaporation of the solvent and purification of the residue over preparative TLC

Sources & evidence

ORD record
ord-62d590930dab42ec89f88cdfee7c81e5
Source dataset
uspto-grants-2014_09
Patent number
US08829030B2

Linked notes

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