Potassium Carbonate → Ethyl 4-methyl-3-(4-(piperidin-1-ylsulfonyl)phenyl)thiophene-2-carboxylate

HRID 1053305Notes

Reaction equation

HRID 1053305 reaction equation
[N:1]1([S:7]([C:10]2[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:19](=O)([O-])[O-].[K+].[K+].Br[C:26]1[C:30]([CH3:31])=[CH:29][S:28][C:27]=1[C:32]([O:34][CH3:35])=[O:33]>C(O)C.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>[CH3:31][C:30]1[C:26]([C:13]2[CH:14]=[CH:15][C:10]([S:7]([N:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)(=[O:9])=[O:8])=[CH:11][CH:12]=2)=[C:27]([C:32]([O:34][CH2:35][CH3:19])=[O:33])[S:28][CH:29]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2808193Methyl 3-bromo-4-methylthiophene-2-carboxylateHCID 44119543(4-(Piperidin-1-ylsulfonyl)phenyl)boronic acid

Product 1

HCID 68286479Ethyl 4-methyl-3-(4-(piperidin-1-ylsulfonyl)phenyl)thiophene-2-carboxylateYield 62%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

(4-(Piperidin-1-ylsulfonyl)phenyl)boronic acid (Prepared according to the procedure reported in US20060258670, 4.41 g, 16.38 mmol) and Potassium carbonate (5.15 g, 37.2 mmol) were added to a stirred suspension of methyl 3-bromo-4-methylthiophene-2-carboxylate (7a, 3.5 g, 14.89 mmol) in a mixture of 100 ml of ethanol and 30 ml toluene in a tube under a nitrogen atmosphere at room temperature (25° C.). Nitrogen was purged to this suspension for 15 minute at room temperature (25° C.). The reaction mixture was then added tetrakis(triphenylphosphine)palladium(0) (0.86 g, 0.74 mmol) at a temperature of about 25° C. and the tube was sealed. The reaction mixture was then stirred at 105° C. for 15 hours. The progress of the reaction was monitored by TLC. The reaction mixture was then filtered and washed with ethyl acetate (2×50 ml). The combined organic layer was then concentrated under reduced pressure to obtain crude product, which was then purified by column chromatography over silica gel (100-200 mesh) using 45% ethyl acetate in hexanes as an eluent to obtain the title compound (3.5 g, 62.0%).

Workup

  1. customNitrogen was purged to this suspension for 15 minute at room temperature (25° C.)
  2. filtrationThe reaction mixture was then filtered
  3. washwashed with ethyl acetate (2×50 ml)
  4. concentrationThe combined organic layer was then concentrated under reduced pressure
  5. customto obtain crude product, which
  6. customwas then purified by column chromatography over silica gel (100-200 mesh)

Sources & evidence

ORD record
ord-41ac21710b17445a95338c1deed061ab
Source dataset
uspto-grants-2016_07
Patent number
US09393247B2

Reaction notes

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