Ethanol → [2-(4-Ethoxycarbonyl-4-methylpiperidin-1-yl)pyrimidin-5-yl]boronic acid

HRID 626933

Reaction equation

HRID 626933 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([B:8]([OH:10])[OH:9])=[CH:4][N:3]=1.Cl.[CH3:12][C:13]1([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.C(O)C.C(N(CC)CC)C>CO.ClCCl.ClCCl>[CH2:22]([O:21][C:19]([C:13]1([CH3:12])[CH2:18][CH2:17][N:16]([C:2]2[N:7]=[CH:6][C:5]([B:8]([OH:10])[OH:9])=[CH:4][N:3]=2)[CH2:15][CH2:14]1)=[O:20])[CH3:23]

Participants

7

Reactant 4

HCID 702EthanolHCID 8471TriethylamineHCID 19361804Ethyl 4-methylpiperidine-4-carboxylate hydrochlorideHCID 21747362(2-Chloropyrimidin-5-yl)boronic acid

Product 1

HCID 89923723[2-(4-Ethoxycarbonyl-4-methylpiperidin-1-yl)pyrimidin-5-yl]boronic acidYield 61%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
80 °C

Procedure

To 2-chloropyrimidine-5-boronic acid (4.00 g, 25.3 mmol) were added ethyl 4-methylpiperidine-4-carboxylate hydrochloride (4.09 g, 23.9 mmol), ethanol (40 mL) and triethylamine (9.0 mL, 64.0 mmol). The mixture was heated at 80° C. for 3 h before being concentrated in vacuo. The reaction mixture was partitioned between water (100 mL) and ethyl acetate (100 mL), then the aqueous layer was separated and extracted with ethyl acetate (2×100 mL). The organic layers were combined and washed with brine (100 mL), then dried (Na2SO4). The solvent was then removed under reduced pressure and the crude reaction mixture was purified by flash column chromatography on silica (Biotage SNAP 100 g, Isolera). Gradient elution, with 100% dichloromethane to 30% methanol/dichloromethane, afforded the title compound (4.27 g, 43% yield, 74% purity) as a brown oil. LCMS (pH 10): MH+ m/z 294.1, RT 0.652 minutes.

Workup

  1. concentrationbefore being concentrated in vacuo
  2. customThe reaction mixture was partitioned between water (100 mL) and ethyl acetate (100 mL)
  3. customthe aqueous layer was separated
  4. extractionextracted with ethyl acetate (2×100 mL)
  5. washwashed with brine (100 mL)
  6. dry with materialdried (Na2SO4)
  7. customThe solvent was then removed under reduced pressure
  8. customthe crude reaction mixture
  9. customwas purified by flash column chromatography on silica (Biotage SNAP 100 g, Isolera)
  10. washGradient elution

Sources & evidence

ORD record
ord-c481efd5e3b44959ac351b257e6d3236
Source dataset
uspto-grants-2016_04
Patent number
US09309243B2

Linked notes

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