Sodium Carbonate → [6-Chloro-4-(4-cyclohexylsulfamoyl-phenyl)-3-methyl-naphthalen-2-yl]-acetic acid methyl ester

HRID 1468418Notes

Reaction equation

HRID 1468418 reaction equation
[CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13](OS(C(F)(F)F)(=O)=O)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([Cl:24])[CH:11]=2)[CH:6]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.B(O)(O)[C:46]1[CH:51]=[CH:50][C:49]([S:52]([NH:55][CH:56]2[CH2:61][CH2:60][CH2:59][CH2:58][CH2:57]2)(=[O:54])=[O:53])=[CH:48][CH:47]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:46]2[CH:47]=[CH:48][C:49]([S:52](=[O:53])(=[O:54])[NH:55][CH:56]3[CH2:61][CH2:60][CH2:59][CH2:58][CH2:57]3)=[CH:50][CH:51]=2)[C:8]2[C:7](=[CH:12][CH:11]=[C:10]([Cl:24])[CH:9]=2)[CH:6]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 44119413(4-(N-Cyclohexylsulfamoyl)phenyl)boronic acidHCID 86694933(6-Chloro-3-methyl-4-trifluoromethanesulfonyloxy-naphthalen-2-yl)-acetic acid methyl ester

Product 1

HCID 89765344[6-Chloro-4-(4-cyclohexylsulfamoyl-phenyl)-3-methyl-naphthalen-2-yl]-acetic acid methyl esterYield 50%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A stirred solution of (6-chloro-3-methyl-4-trifluoromethanesulfonyloxy-naphthalen-2-yl)-acetic acid methyl ester (0.10 g, 0.25 mmol) in dimethoxyethane (5 mL) was purged with argon for 5 minutes at room temperature. Triphenylphosphine (0.015 g, 0.055 mmol), palladium (II) acetate (0.006 g, 0.027 mmol), 4-N-cyclohexylsulfamoylphenylboronic acid (0.096 g, 0.33 mmol) and a 2 M aqueous solution of sodium carbonate (0.6 mL, 1.2 mmol) were added simultaneously to the reaction mixture at room temperature under argon. The reaction mixture was refluxed for 2 hours and then cooled to room temperature. Water was added and the mixture was extracted twice with ethyl acetate. The collected organic extracts were washed with water and then brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the crude product, which was finally purified using flash chromatography (Biotage, 5-10% ethyl acetate-hexane) to afford [6-chloro-4-(4-cyclohexylsulfamoyl-phenyl)-3-methyl-naphthalen-2-yl]-acetic acid methyl ester (0.06 g, 50%) as a solid. MS calcd. for C26H27ClNO4S [(M−H)−] 484, obsd. 484.4.

Workup

  1. temperatureThe reaction mixture was refluxed for 2 hours
  2. extractionthe mixture was extracted twice with ethyl acetate
  3. washThe collected organic extracts were washed with water
  4. dry with materialbrine, dried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customto give the crude product, which
  7. customwas finally purified

Sources & evidence

ORD record
ord-e3bdde096dcb43b4a02d9e9b11c20a23
Source dataset
uspto-grants-2015_04
Patent number
US09000044B2

Reaction notes

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