Sodium Carbonate → tert-Butyl 4-(4-(5-chloro-2-hydroxyphenyl)pyridin-2-yl)piperazine-1-carboxylate

HRID 1619718Notes

Reaction equation

HRID 1619718 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[CH:3]=1.[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([OH:31])=[C:26](B(O)O)[CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([OH:31])=[C:24]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([N:8]3[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]3)[CH:3]=2)[CH:23]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 23005362(5-Chloro-2-hydroxyphenyl)boronic Acid (contains varying amounts of Anhydride)HCID 53217365tert-Butyl 4-(4-bromopyridin-2-yl)piperazine-1-carboxylate

Product 1

HCID 136063613tert-Butyl 4-(4-(5-chloro-2-hydroxyphenyl)pyridin-2-yl)piperazine-1-carboxylateYield 67.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
70 °C

Procedure

tert-Butyl 4-(4-bromopyridin-2-yl)piperazine-1-carboxylate (1.00 g, 2.66 mmol), 5-chloro-2-hydroxyphenylboronic acid (458 mg, 2.66 mmol) and sodium carbonate (1.13 g, 10.64 mmol) were combined and dissolved in a mixture of dioxane/water (14 mL/4 mL). The reaction mixture was degassed for 20 min with nitrogen and then tetrakistriphenylphosphinepalladium (0) (153 mg, 0.133 mmol) was added. The reaction mixture was heated at 70° C. for 18 hours and then partitioned between ethyl acetate (20 mL) and water (10 mL). The organic layer was separated, washed with brine (10 mL), dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was purified on silica gel by Biotage™ (10% to 60% ethyl acetate in heptane over 20 CV) to give the title compound (700 mg, 66%) as a white solid.

Workup

  1. customThe reaction mixture was degassed for 20 min with nitrogen
  2. custompartitioned between ethyl acetate (20 mL) and water (10 mL)
  3. customThe organic layer was separated
  4. washwashed with brine (10 mL)
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified on silica gel by Biotage™ (10% to 60% ethyl acetate in heptane over 20 CV)

Sources & evidence

ORD record
ord-9cf49f09c04649cfa63e7fb5ab4563c1
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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