1,2-Dimethoxyethane → HCID 68746268, compound

HRID 885109Notes

Reaction equation

HRID 885109 reaction equation
[CH2:1]([N:3]1[CH2:8][CH2:7][C:6]([C:10]2[S:11][C:12](I)=[CH:13][N:14]=2)([OH:9])[CH2:5][CH2:4]1)[CH3:2].[C:16]([O:20][C:21]([NH:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][C:25]=1[F:33])=[O:22])([CH3:19])([CH3:18])[CH3:17].[F-].[Cs+].C(COC)OC>C(OCC)(=O)C.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.CO>[C:16]([O:20][C:21](=[O:22])[NH:23][C:24]1[CH:29]=[CH:28][C:27]([C:12]2[S:11][C:10]([C:6]3([OH:9])[CH2:7][CH2:8][N:3]([CH2:1][CH3:2])[CH2:4][CH2:5]3)=[N:14][CH:13]=2)=[CH:26][C:25]=1[F:33])([CH3:19])([CH3:17])[CH3:18]

Participants

9

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 25953Cesium fluorideHCID 22288677{4-[(tert-Butoxycarbonyl)amino]-3-fluorophenyl}boronic acidHCID 68720463HCID 68720463, compound

Product 1

HCID 68746268HCID 68746268, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A solution of Example 2A (0.33 g, 0.98 mmol), 4-(tert-butoxycarbonylamino)-3-fluorophenylboronic acid (0.25 g, 0.98 mmol), CsF (0.46 g, 3.0 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.12 g, 0.098 mmol) in a solvent mixture of dimethoxyethane (2 mL) and methanol (1 mL) was heated to 90° C. for 16 h. The reaction was cooled to ambient temperature and diluted with ethyl acetate (5 mL) and H2O (5 mL). The layers were separated, and the organic was washed with 10% aqueous HCl (3×15 mL). 2N NaOH was added to the combined acidic aqueous layers until pH=8. The aqueous layer was extracted with ethyl acetate (3×15 mL). The extracts were then dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give the title product as a solid. MS (ESI) m/z 422 [M+H]+.

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. customThe layers were separated
  3. washthe organic was washed with 10% aqueous HCl (3×15 mL)
  4. addition2N NaOH was added to the combined acidic aqueous layers until pH=8
  5. extractionThe aqueous layer was extracted with ethyl acetate (3×15 mL)
  6. dry with materialThe extracts were then dried with anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9e3f1bb4cc4146ffb1bb0d8adc146db8
Source dataset
uspto-grants-2012_08
Patent number
US08242139B2

Reaction notes

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