Cesium carbonate → HCID 59275495, compound

HRID 1025174Notes

Reaction equation

HRID 1025174 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[C:22]([CH3:39])=[CH:23][C:24](OS(C(F)(F)F)(=O)=O)=[C:25]([CH:30]=4)[C:26]([O:28][CH3:29])=[O:27])=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:4][CH:3]=1.O1CCOCC1.[Cl:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][C:48]=1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C.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.O>[Cl:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][C:48]=1[C:24]1[C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:30][C:21]([C:18]2[CH:19]=[CH:20][C:10]3[O:9][C:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)=[C:12]([C:13](=[O:16])[NH:14][CH3:15])[C:11]=3[CH:17]=2)=[C:22]([CH3:39])[CH:23]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 27343222-Chlorophenylboronic acidHCID 86640861HCID 86640861, compound

Product 1

HCID 59275495HCID 59275495, compoundYield 90.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a small sealed tube was added methyl 5-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methyl-2-(trifluoromethylsulfonyloxy)benzoate (67.3 mg, 0.1 mmol), dioxane (3 mL), water (0.600 mL), 2-chlorophenylboronic acid (18.76 mg, 0.120 mmol), cesium carbonate (32.6 mg, 0.100 mmol) and tetrakis(triphenylphosphine)palladium(0) (2.311 mg, 2.000 mmol). The tube was sealed and heated overnight at 80° C. The reaction was cooled to room temperature, filtered through a plug of celite and concentrated to near dryness under a stream of nitrogen. The crude reaction mixture was taken up in 6 mL of acetonitrile and purified using a Shimadzu preparative HPLC employing acetonitrile/water/trifluoroacetic acid where solvent A was 10% acetonitrile/90% water/0.1% trifluoroacetic acid and solvent B was 10% water/90% acetonitrile/0.1% trifluoroacetic acid with a Waters Sunfire 3.5 μm C18 19×150 mm column at a gradient of 30-100% B and a flow rate of 25 mL/min. over 20 minutes with a 10 minute hold. The solvent was removed giving 48 mgs (89% yield) of methyl 2′-chloro-4-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-5-methylbiphenyl-2-carboxylate as a white solid. The LC/MS data was obtained on a Shimadzu analytical LC/Micromass Platform LC (ESI+) at 220 nm using the following set of conditions: Phenomenex Luna 3 μm C18, 2×50 mm column, with a gradient of 0-100% B (B=90% HPLC grade acetonitrile/0.1% trifluoroacetic acid/10% HPLC grade water), (A=90% HPLC grade water/0.1% trifluoroacetic acid/10% HPLC grade acetonitrile), in 4 minutes with a 1 minute hold at a rate of 0.8 mL/minute. 1H NMR (500 MHz, THF-d8) δ ppm 2.35 (s, 3 H), 2.91 (d, J=4.58 Hz, 3H), 3.57 (s, 3 H), 7.21-7.26 (m, 3 H), 7.27-7.30 (m, 1 H), 7.30-7.34 (m, 2 H), 7.38 (dd, J=8.39, 1.68 Hz, 1 H), 7.41-7.44 (m, 1 H), 7.50 (d, J=4.27 Hz, 1 H), 7.63 (d, J=8.24 Hz, 1 H), 7.75 (d, J=1.53 Hz, 1 H), 7.92 (s, 1 H), 8.13-8.19 (m, 2 H). LCMS m/z 528.4 (M+H), Rt=4.036 min., 98.3% purity.

Workup

  1. customThe tube was sealed
  2. temperatureThe reaction was cooled to room temperature
  3. filtrationfiltered through a plug of celite
  4. concentrationconcentrated
  5. customThe crude reaction mixture
  6. custompurified
  7. customThe solvent was removed

Sources & evidence

ORD record
ord-20ed4757bc4f4718b2cf5fc53edf85c7
Source dataset
uspto-grants-2014_05
Patent number
US08722688B2

Reaction notes

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