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

HRID 1780339Notes

Reaction equation

HRID 1780339 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 chloroform. The CHCl3 was removed under reduced pressure, and the residue was chromatographed on a silica gel column, eluting with ethyl acetate/hexane 1:1 to afford the title compound (280 mg). MS (DCI/NH3) m/z 375 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.40 (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 chloroform
  4. customThe CHCl3 was removed under reduced pressure
  5. customthe residue was chromatographed on a silica gel column
  6. washeluting with ethyl acetate/hexane 1:1

Sources & evidence

ORD record
ord-7e585821912c49238664860b321734a5
Source dataset
uspto-grants-1997_05
Patent number
US05629325

Reaction notes

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