Sodium Carbonate → HCID 69157497, compound

HRID 1294391Notes

Reaction equation

HRID 1294391 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:10][CH:9]2[C:11]([O:13][CH3:14])=[O:12])=[C:4]([F:15])[CH:3]=1.[F:16][C:17]([F:49])([F:48])[CH2:18][NH:19][C:20]([C:22]1[C:31](=[O:32])[C:30]2[C:25](=[N:26][CH:27]=[CH:28][CH:29]=2)[N:24]([C:33]2[CH:38]=[CH:37][CH:36]=[C:35](B3OC(C)(C)C(C)(C)O3)[CH:34]=2)[CH:23]=1)=[O:21].CN(C)C1C=CC=CC=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.CC(O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:15][C:4]1[CH:3]=[C:2]([C:35]2[CH:36]=[CH:37][CH:38]=[C:33]([N:24]3[C:25]4[C:30](=[CH:29][CH:28]=[CH:27][N:26]=4)[C:31](=[O:32])[C:22]([C:20]([NH:19][CH2:18][C:17]([F:48])([F:49])[F:16])=[O:21])=[CH:23]3)[CH:34]=2)[CH:7]=[CH:6][C:5]=1[CH:8]1[CH2:10][CH:9]1[C:11]([O:13][CH3:14])=[O:12]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 69157593(+)-Methyl 2-(4-bromo-2-fluorophenyl)cyclopropanecarboxylateHCID 69159248HCID 69159248, compound

Product 1

HCID 69157497HCID 69157497, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 20197112Isopropanol dimethylformamideSolvent

Procedure

To a solution of (+)-methyl 2-(4-bromo-2-fluorophenyl)cyclopropanecarboxylate from step 8 (1.2 eq) and boronate ester from step 4 (1 eq) in DMF-iPrOH (1:1, 0.1M), was added tris(dibenzylideneacetone)dipalladium(0) (0.055 eq), 2-(dimethylamino)-2′-(dicyclohexylphosphino)biphenyl (0.13 eq) and a sodium carbonate solution (2M, 4 eq) The reaction mixture was heated at 78° C. for 2 h. The reaction mixture was filtered on Celite and silica gel (1:1) and washed with EtOAc. The filtrate was concentrated in vacuo and remaining solvents were distilled in vacuo. The resulting yellow solid is stirred vigourously in ether. The residue then isolated by filtration and washed with ether. Mother liquors were further purified by flash chromatography (toluene/EtOAc, 100:0 to 70:30).

Workup

  1. filtrationThe reaction mixture was filtered on Celite and silica gel (1:1)
  2. washwashed with EtOAc
  3. concentrationThe filtrate was concentrated in vacuo
  4. distillationwere distilled in vacuo
  5. customThe residue then isolated by filtration
  6. washwashed with ether
  7. customMother liquors were further purified by flash chromatography (toluene/EtOAc, 100:0 to 70:30)

Sources & evidence

ORD record
ord-7758adbfb2fb40888306503446f978c7
Source dataset
uspto-grants-2007_07
Patent number
US07238706B2

Reaction notes

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