Cesium fluoride → HCID 67080432, compound

HRID 1021397Notes

Reaction equation

HRID 1021397 reaction equation
Br[C:2]1[CH:35]=[CH:34][C:5]([CH2:6][CH2:7][NH:8][C:9]([C:11]2[CH:33]=[CH:32][C:14]([O:15][C:16]3[CH:25]=[C:24]4[C:19]([CH:20]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:21][CH2:22][O:23]4)=[CH:18][C:17]=3[Cl:31])=[CH:13][CH:12]=2)=[O:10])=[CH:4][CH:3]=1.[Cl:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1B(O)O.[F-].[Cs+]>COCCOC.CO.O.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>[Cl:31][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][C:16]=1[O:15][C:14]1[CH:32]=[CH:33][C:11]([C:9](=[O:10])[NH:8][CH2:7][CH2:6][C:5]3[CH:34]=[CH:35][C:2]([C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=4[Cl:36])=[CH:3][CH:4]=3)=[CH:12][CH:13]=1)[O:23][CH2:22][CH2:21][CH:20]2[C:26]([O:28][CH2:29][CH3:30])=[O:27]

Participants

8

Reactant 3

HCID 25953Cesium fluorideHCID 27343222-Chlorophenylboronic acidHCID 67080410Ethyl 7-(4-(4-bromophenethylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate

Product 1

HCID 67080432HCID 67080432, compoundYield 59.3%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a stirred suspension of ethyl 7-(4-(4-bromophenethylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate (0.56 g, 1.0 mmol) and 2-chlorophenylboronic acid (0.17 g, 1.1 mmol) in a mixture of 1,2-dimethoxyethane (4 mL) and methanol (2 mL) was added cesium fluoride (0.30 g, 2.0 mmol), followed by tetrakis(triphenylphosphine)palladium(0) (0.035 g, 0.03 mmol). The resulting mixture was stirred in an oil bath set to 80° C. for 1 hour. The mixture was cooled to ambient temperature and diluted with water (20 mL) and extracted with dichloromethane (2×20 mL). The organic layers were combined and dried over sodium sulfate, then concentrated. The residue was purified by chromatography on silica gel, eluting with 80/20 hexanes/ethyl acetate, to afford ethyl 6-chloro-7-(4-(2-(2′-chlorobiphenyl-4-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylate as a light brown oil (0.35 g, 59% yield).

Workup

  1. extractionextracted with dichloromethane (2×20 mL)
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by chromatography on silica gel
  5. washeluting with 80/20 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-014ab9974e0a4b7eb4e7c65e58705469
Source dataset
uspto-grants-2014_05
Patent number
US08716498B2

Reaction notes

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