Phenylboronic Acid → 5-Phenyl-6-chloro-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine

HRID 2305123Notes

Reaction equation

HRID 2305123 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:9][CH2:10][C@@H:11]2[CH2:14][CH2:13][N:12]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:5]=[N:6][C:7]=1[Cl:8].[C:22]1(B(O)O)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1>[C:22]1([C:2]2[CH:3]=[C:4]([O:9][CH2:10][C@@H:11]3[CH2:14][CH2:13][N:12]3[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:5]=[N:6][C:7]=2[Cl:8])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 66827Phenylboronic AcidHCID 516892Sodium BicarbonateHCID 228726673-(1-BOC-2-(S)-azetidinylmethoxy)-5-bromo-6-chloropyridine

Product 1

HCID 228726875-Phenyl-6-chloro-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridineYield 74.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

5-bromo-6-chloro-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine from Example 66a (375 mg, 1 mmol), phenylboronic acid (146 mg, 1.2 mmol) and Pd(0) (35 mg) were mixed together in toluene (2 mL), and the mixture was heated at reflux for 16 hours. NaHCO3 solution (2%, 1 mL) was added, and the mixture was extracted with CHCl3. The CHCl3 was removed under reduced pressure, and the residue was chromatographed on a silica gel column, eluting with EtOAc/hexane 1:1 to afford the title compound (280 mg). MS (CI/NH3) m/z 375 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ 1.40 (s, 9H), 2.33-2.43 (m, 2H), 3.29 (t, J=7.5 Hz, 2H), 4.15 (dd, J=2.5, 7.5 Hz, 1H), 4.32-4.42 (m, 1H), 4.48-4.57 (m, 1H), 7.25-7.29 (m, 4H), 7.28 (d, J=2 Hz, 1H), 7.42-7.48 (m, 5H), 8.12 (d, J=3 Hz, 1H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 16 hours
  3. extractionthe mixture was extracted with CHCl3
  4. customThe CHCl3 was removed under reduced pressure
  5. customthe residue was chromatographed on a silica gel column
  6. washeluting with EtOAc/hexane 1:1

Sources & evidence

ORD record
ord-ba71168eb0214464b026e2d1a8e8682f
Source dataset
uspto-grants-2002_08
Patent number
US06437138B1

Reaction notes

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