Cesium carbonate → HCID 23571070, compound

HRID 1823988Notes

Reaction equation

HRID 1823988 reaction equation
Br[C:2]1[N:3]=[CH:4][N:5]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[CH:6]=1.CC1(C)C(C)(C)OB([C:22]2[CH:23]=[CH:24][C:25]3[CH2:32][C@H:31]4[C@:33]5([CH2:37][N:36]([CH2:38][C:39]([F:42])([F:41])[F:40])[S:35](=[O:44])(=[O:43])[NH:34]5)[C@H:28]([CH2:29][CH2:30]4)[CH2:27][C:26]=3[CH:45]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.O.C(OCC)(=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:13][C:10]1[CH:11]=[CH:12][C:7]([N:5]2[CH:6]=[C:2]([C:22]3[CH:23]=[CH:24][C:25]4[CH2:32][C@H:31]5[C@:33]6([CH2:37][N:36]([CH2:38][C:39]([F:42])([F:41])[F:40])[S:35](=[O:43])(=[O:44])[NH:34]6)[C@H:28]([CH2:29][CH2:30]5)[CH2:27][C:26]=4[CH:45]=3)[N:3]=[CH:4]2)=[CH:8][CH:9]=1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 221480334-Bromo-1-(4-fluorophenyl)-1H-imidazoleHCID 23571079[6s,9r,11r]2',3',4',5,5',6,7,8,9,10-Decahydro-2-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-5'-(2,2,2-trifluoroethyl)spiro[6,9-methanobenzocyclooctene-11,3'-[1,2,5]thiadiazole]1',1'-dioxide

Product 1

HCID 23571070HCID 23571070, compoundYield 12%

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a degassed solution of 4-bromo-1-(4-fluorophenyl)imidazole from Step 1 (50 mg, 0.21 mmol) and the homochiral boronate from Example 24 Step 1 (100 mg. 0.21 mmol) in N,N-dimethylformamide (3 mL) and water (1 mL) was added cesium carbonate (67 mg, 0.21 mmol) followed by tetrakis(triphenylphosphine) palladium (0) (24 mg, 0.02 mmol). The reaction was heated at 100° C. for 19 hours. The cooled reaction mixture was diluted with ethyl acetate. The organic layer was washed with water (×3) and brine, dried (MgSO4) and concentrated. The residue was purified by flash chromatography on silica eluting with ethyl acetate/isohexane (gradient 20 to 30 to 50% to neat ethyl acetate) followed by recrystallisation from dichloromethane/diethyl ether to give the product (13 mg, 12%).

Workup

  1. customThe cooled reaction mixture
  2. washThe organic layer was washed with water (×3) and brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography on silica eluting with ethyl acetate/isohexane (gradient 20 to 30 to 50% to neat ethyl acetate)
  6. customfollowed by recrystallisation from dichloromethane/diethyl ether

Sources & evidence

ORD record
ord-06cdbf6020774c1d8a7b54d0c03fb354
Source dataset
uspto-grants-2006_05
Patent number
US07041689B2

Reaction notes

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