Morpholine → HCID 68733191, compound

HRID 888390Notes

Reaction equation

HRID 888390 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:16]([O:18]C)=[O:17])[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][C:9]=2[F:15])[CH:7]=1.[NH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[OH-].[Na+]>CN(C)C(=O)C.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.[Pd].CO>[F:15][C:9]1[CH:10]=[C:11]([CH3:14])[CH:12]=[CH:13][C:8]=1[C:6]1[CH:7]=[C:2]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[CH:3]=[C:4]([C:16]([OH:18])=[O:17])[CH:5]=1

Participants

9

Reactant 5

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 68499851HCID 68499851, compound

Product 1

HCID 68733191HCID 68733191, compound

Reagents, catalysts & solvents 3

HCID 72499888Dibenzalacetone palladiumCatalystHCID 887MethanolSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 5-bromo-2′-fluoro-4′-methylbiphenyl-3-carboxylate (408.0 mg, 1.263 mmol) in N,N-dimethylacetamide (5 mL) was added morpholine (0.17 mL, 1.9 mmol), cesium carbonate (1.23 g, 3.79 mmol), palladium dibenzylidene acetone (116.0 mg, 0.13 mmol), and 2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′biphenyl (XPhos; 90.0 mg, 0.19 mmol) and the mixture heated to 100° C. After 16 h the reaction was allowed to cool to ambient temperature, filtered with methanol, and sodium hydroxide (1M in water; 3.0 mL, 3.0 mmol) was added. After 16 h, reaction was concentrated, acidified with trifluoroacetic acid, and purified by reverse phase HPLC (C-18, 95% water/acetonitrile→20% water/acetonitrile with 0.1% trifluoroacetic acid). Extraction with dichloromethane and 1M aqueous hydrochloric acid gave the title compound. MS 316.1 (M+1).

Workup

  1. temperatureto cool to ambient temperature
  2. additionwas added
  3. waitAfter 16 h
  4. customreaction
  5. concentrationwas concentrated
  6. custompurified by reverse phase HPLC (C-18, 95% water/acetonitrile→20% water/acetonitrile with 0.1% trifluoroacetic acid)
  7. extractionExtraction with dichloromethane and 1M aqueous hydrochloric acid

Sources & evidence

ORD record
ord-b791034f7ed04c2c90d0f383a922c005
Source dataset
uspto-grants-2012_08
Patent number
US08247401B2

Reaction notes

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