Sodium Carbonate → HCID 59323812, compound

HRID 1911502Notes

Reaction equation

HRID 1911502 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][O:11][C:10]([NH2:13])=[N:9]2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[Na+].[Na+].[F:20][C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1>COCCOC.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:2]2[CH:7]=[CH:6][C:5]([CH:8]3[CH2:12][O:11][C:10]([NH2:13])=[N:9]3)=[CH:4][CH:3]=2)=[CH:23][CH:22]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 59323892HCID 59323892, compound

Product 1

HCID 59323812HCID 59323812, compoundYield 54.1%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

To a stirred solution of (RS)-4-(4-bromo-phenyl)-4,5-dihydro-oxazol-2-ylamine (80 mg; example 20) at r.t. in 1,2-dimethoxyethane (4 ml) under an argon atmosphere were added PdCl2(dppf) (24 mg), 10% aq. Na2CO3 (1 ml) and 4-fluorophenylboronic acid (186 mg). The mixture was heated to 85° C. and stirring at that temperature was continued for 18 h. The dark brown mixture was cooled to r.t., diluted with EtOAc and washed with H2O. The aqueous phase was back extracted with EtOAc. The combined organics were washed with H2O and brine, dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography (SiO2; gradient: CH2Cl2->CH2Cl2/MeOH 9:1) to give (RS)-4-(4′-fluoro-biphenyl-4-yl)-4,5-dihydro-oxazol-2-ylamine (46 mg) as off-white solid. MS (ISP): 257.0 ([M+H]+)

Workup

  1. temperatureThe dark brown mixture was cooled to r.t.
  2. washwashed with H2O
  3. extractionThe aqueous phase was back extracted with EtOAc
  4. washThe combined organics were washed with H2O and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by column chromatography (SiO2; gradient: CH2Cl2->CH2Cl2/MeOH 9:1)

Sources & evidence

ORD record
ord-0e62f917d7bc4cca886176e2214cef92
Source dataset
uspto-grants-2013_12
Patent number
US08604061B2

Reaction notes

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