Cesium carbonate → Methyl 2-(6-(tert-butoxycarbonylamino)-5-fluoropyridin-3-yloxy)-4-fluorobenzoate

HRID 573113Notes

Reaction equation

HRID 573113 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([O:8][C:9]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:10]=2[C:11]([O:13][CH3:14])=[O:12])=[CH:4][C:3]=1[F:20].[C:21](=[O:28])([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH2:22].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>C(O[Pd]OC(=O)C)(=O)C.O1CCOCC1>[C:24]([O:23][C:21]([NH:22][C:2]1[N:7]=[CH:6][C:5]([O:8][C:9]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:10]=2[C:11]([O:13][CH3:14])=[O:12])=[CH:4][C:3]=1[F:20])=[O:28])([CH3:27])([CH3:26])[CH3:25]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86642876Methyl 2-(6-chloro-5-fluoropyridin-3-yloxy)-4-fluorobenzoate

Product 1

HCID 67226334Methyl 2-(6-(tert-butoxycarbonylamino)-5-fluoropyridin-3-yloxy)-4-fluorobenzoate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

Methyl 2-(6-chloro-5-fluoropyridin-3-yloxy)-4-fluorobenzoate (0.875 g), tert-butyl carbamate (0.410 g), cesium carbonate (1.427 g), diacetoxypalladium (0.033 g) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.169 g) were added to dioxane (10 mL). The reaction was degassed with nitrogen then sealed. The reaction was then heated to 85° C. After stirring for 16 hours the reaction was cooled, diluted with water (25 mL) and the product was extracted into dichloromethane (2×25 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated. Silica gel chromatography (GraceResolv 40 g) eluting with a gradient of 5% to 25% ethyl acetate/hexanes gave the title compound.

Workup

  1. customThe reaction was degassed with nitrogen
  2. customthen sealed
  3. temperaturewas cooled
  4. additiondiluted with water (25 mL)
  5. extractionthe product was extracted into dichloromethane (2×25 mL)
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washSilica gel chromatography (GraceResolv 40 g) eluting with a gradient of 5% to 25% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-345bdff0571d4c0c8cb27ff1a0aa6081
Source dataset
uspto-grants-2015_05
Patent number
US09029404B2

Reaction notes

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