Cesium carbonate → HCID 89813930, compound

HRID 2172337Notes

Reaction equation

HRID 2172337 reaction equation
Br.Br[C:3]1[C:12]2[CH2:11][CH2:10][NH:9][CH2:8][C:7]=2[N:6]=[CH:5][CH:4]=1.[CH3:13][O:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>C(Cl)Cl.ClCCl.[Pd+2].ClC1C=C[C-](P(C2C=CC=CC=2)C2C=CC=CC=2)C=1Cl.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[CH3:13][O:14][C:15]1[CH:20]=[C:19]([C:21]([F:22])([F:23])[F:24])[CH:18]=[CH:17][C:16]=1[C:3]1[C:12]2[CH2:11][CH2:10][NH:9][CH2:8][C:7]=2[N:6]=[CH:5][CH:4]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 24901776(2-Methoxy-4-(trifluoromethyl)phenyl)boronic acidHCID 898151471454668-10-0

Product 1

HCID 89813930HCID 89813930, compoundYield 66.9%

Reagents, catalysts & solvents 3

HCID 178478475HCID 178478475, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

A pressure vessel was charged with 4-bromo-5,6,7,8-tetrahydro-1,7-naphthyridine hydrobromide (331 mg, 1.126 mmol), 2-methoxy-4-(trifluoromethyl)phenylboronic acid (488 mg, 2.219 mmol), cesium carbonate, 99.9% (metal basis) (0.275 mL, 3.44 mmol), and dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium (ii) dichloromethane adduct (86 mg, 0.105 mmol). Dioxane (2 mL) and water (0.4 mL) were added, and argon was streamed into the vessel for about 20 seconds. The mixture was stirred in a 70° C. oil bath for two hours, then diluted with CH2Cl2 and washed with H2O. The layers were separated and the water layer was extracted with another portion of CH2Cl2. The combined organic layers were dried over Na2SO4 and concentrated. The residue was purified by column chromatography (Combiflash, 40 gram Redisep gold column), eluting with 0-100% (3:1 EtoAc/EtOH with 2% NH4OH in heptane) to obtain 4-(2-methoxy-4-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydro-1,7-naphthyridine (232 mg, 0.753 mmol, 66.8% yield) as a brown viscous oil. [M+H]+=309.0.

Workup

  1. washwashed with H2O
  2. customThe layers were separated
  3. extractionthe water layer was extracted with another portion of CH2Cl2
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (Combiflash, 40 gram Redisep gold column)
  7. washeluting with 0-100% (3:1 EtoAc/EtOH with 2% NH4OH in heptane)

Sources & evidence

ORD record
ord-c491bd5ac2c24b84b06e123cd5da38c3
Source dataset
uspto-grants-2015_06
Patent number
US09051311B2

Reaction notes

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