Cesium carbonate → methyl 6-[bis-(tert-butoxycarbonyl)amino]-3-[2-(tetrahydropyran-2-yl)-2H-pyrazol-3-yl]-2-vinylbenzoate

HRID 595108Notes

Reaction equation

HRID 595108 reaction equation
[C:1]([O:5][C:6]([N:8]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[C:9]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[C:13](OS(C(F)(F)F)(=O)=O)[C:12]([C:27]2[N:28]([CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][O:33]3)[N:29]=[CH:30][CH:31]=2)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:45](B1OC(C)(C)C(C)(C)O1)=[CH2:46].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:41]([O:40][C:38]([N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[C:9]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[C:13]([CH:45]=[CH2:46])[C:12]([C:27]2[N:28]([CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][O:33]3)[N:29]=[CH:30][CH:31]=2)=[CH:11][CH:10]=1)=[O:39])([CH3:43])([CH3:44])[CH3:42]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86712819methyl 6-[bis-(tert-butoxycarbonyl)amino]-3-[2-(tetrahydropyran-2-yl)-2H-pyrazol-3-yl]-2-trifluoromethanesulfonyloxybenzoate2×

Product 1

HCID 86712818methyl 6-[bis-(tert-butoxycarbonyl)amino]-3-[2-(tetrahydropyran-2-yl)-2H-pyrazol-3-yl]-2-vinylbenzoate

Reagents, catalysts & solvents 3

HCID 178419050HCID 178419050, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of methyl 6-[bis-(tert-butoxycarbonyl)amino]-3-[2-(tetrahydropyran-2-yl)-2H-pyrazol-3-yl]-2-trifluoromethanesulfonyloxybenzoate (Intermediate 11, 4.35 g), vinylboronic acid pinacol ester (1.9 mL), bis(triphenylphosphine)palladium (II) dichloride (0.255 g) and cesium carbonate (7.1 g) in dioxane (300 mL) and water (47 mL) was de-gassed and purged with nitrogen. The mixture was then heated to 80° C. for 4 hours. After cooling, the mixture was diluted with ether and the organic layer was separated, dried (MgSO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-60% to give methyl 6-[bis-(tert-butoxycarbonyl)amino]-3-[2-(tetrahydropyran-2-yl)-2H-pyrazol-3-yl]-2-vinylbenzoate (2.84 g) as a gum.

Workup

  1. customwas de-gassed
  2. custompurged with nitrogen
  3. temperatureAfter cooling
  4. additionthe mixture was diluted with ether
  5. customthe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe residue was purified by chromatography on silica
  10. washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-60%

Sources & evidence

ORD record
ord-f0bbfa1577ad412a98829974b58e469a
Source dataset
uspto-grants-2016_01
Patent number
US09242997B2

Reaction notes

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