Cesium carbonate → HCID 90347084, compound

HRID 590613Notes

Reaction equation

HRID 590613 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1)#[N:2].FC(F)(F)S(O[C:18]1[O:36][CH2:35][C@:21]2([C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=3[F:44])[N:22]=[C:23]([NH:26][C:27](=[O:34])[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[S:24][CH2:25][C@@H:20]2[CH:19]=1)(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:18]2[O:36][CH2:35][C@:21]3([C:37]4[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=4[F:44])[N:22]=[C:23]([NH:26][C:27](=[O:34])[C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[S:24][CH2:25][C@@H:20]3[CH:19]=2)=[CH:5][CH:4]=1)#[N:2]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27343264-Cyanophenylboronic acidHCID 90331770HCID 90331770, compound

Product 1

HCID 90347084HCID 90347084, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

(4-Cyanophenyl)boronic acid (55 mg, 0.37 mmol, 2.0 equiv) was added to a solution of (4aR,8aS)-2-(benzoylamino)-8a-(2,4-difluorophenyl)-4,4a,8,8a-tetrahydropyrano[3,4-d][1,3]thiazin-6-yl trifluoromethanesulfonate (P4) (100 mg, 0.19 mmol, 1.0 equiv) in tetrahydrofuran (1.5 mL). An aqueous 2 M solution of cesium carbonate (0.47 mL, 0.935 mmol, 5.0 equiv) and dichlorobis(triphenylphosphine)palladium(II) (6.4 mg, 9 μmol, 0.05 equiv) were added. The reaction was de-gassed and stirred at 65° C. for 17 hours. The reaction mixture was partitioned between water (10 mL) and ethyl acetate (20 mL) and the organic layer separated. The extraction was repeated twice and the combined organics were washed with saturated aqueous sodium chloride solution (10 mL), dried over sodium sulfate, filtered and concentrated in vacuo. Chromatography on silica gel (Gradient: 0% to 50% ethyl acetate in heptane) afforded the product as a white solid. Yield: 64 mg, 70%. LCMS m/z 488.3 [M+H+].

Workup

  1. customThe reaction was de-gassed
  2. customThe reaction mixture was partitioned between water (10 mL) and ethyl acetate (20 mL)
  3. customthe organic layer separated
  4. extractionThe extraction
  5. washthe combined organics were washed with saturated aqueous sodium chloride solution (10 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-698a74afc28c49fe9995a851530ba9dc
Source dataset
uspto-grants-2016_01
Patent number
US09233981B1

Reaction notes

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