Sodium Carbonate → HCID 21905722, compound

HRID 1247296Notes

Reaction equation

HRID 1247296 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([O:21][CH3:22])[C:9]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]#[N:20])=[CH:15][CH:14]=2)=[O:10])=[C:4]([F:23])[CH:3]=1.C([O-])([O-])=O.[Na+].[Na+].[CH3:30][N:31]([CH3:41])[C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1>COCCOC.C(OCC)(=O)C.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]>[C:19]([C:16]1[CH:17]=[CH:18][C:13]([CH2:12][NH:11][C:9](=[O:10])[CH:8]([C:5]2[CH:6]=[CH:7][C:2]([C:35]3[CH:36]=[CH:37][C:32]([N:31]([CH3:41])[CH3:30])=[CH:33][CH:34]=3)=[CH:3][C:4]=2[F:23])[O:21][CH3:22])=[CH:14][CH:15]=1)#[N:20]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343444-(Dimethylamino)phenylboronic acidHCID 21905621HCID 21905621, compound

Product 1

HCID 21905722HCID 21905722, compoundYield 87.2%

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)-2-(4-bromo-2-fluoro-phenyl)-N-(4-cyano-benzyl)-2-methoxy-acetamide (example 41.2, 173 mg) in 1,2-dimethoxyethane (8 ml) were added PdCl2(dppf) (34 mg), an aqueous 10% solution of Na2CO3 (2 ml) and 4-dimethylaminophenylboronic acid (378 mg). The mixture was then stirred at 85° C. under an argon atmosphere for 1.5 h. After cooling to rt, the mixture was diluted with ethyl acetate (15 ml) and washed with water (10 ml). The aqueous layer was extracted with ethyl acetate and the combined organics were washed with water and brine, dried (MgSO4), filtered and concentrated. The product was purified by chromatography (silica gel, gradient cyclohexane=>cyclohexane/ethyl acetate 2:3) to give (RS)-N-(4-cyano-benzyl)-2-(4′-dimethylamino-3-fluoro-biphenyl-4-yl)-2-methoxy-acetamide (167 mg) as a light yellow solid.

Workup

  1. temperatureAfter cooling to rt
  2. washwashed with water (10 ml)
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. washthe combined organics were washed with water and brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe product was purified by chromatography (silica gel, gradient cyclohexane=>cyclohexane/ethyl acetate 2:3)

Sources & evidence

ORD record
ord-4439b677ea874233a77c77739bd1345a
Source dataset
uspto-grants-2006_10
Patent number
US07129238B2

Reaction notes

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