Sodium Carbonate → 3-(2-(S)-Azetidinylmethoxy)-6-chloro-5-(4-chlorophenyl)pyridine

HRID 365864Notes

Reaction equation

HRID 365864 reaction equation
C([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[N:16][C:17]([Cl:21])=[C:18](Br)[CH:19]=1)(OC(C)(C)C)=O.[Cl:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1>[NH:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[N:16][C:17]([Cl:21])=[C:18]([C:26]2[CH:27]=[CH:28][C:23]([Cl:22])=[CH:24][CH:25]=2)[CH:19]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 228726673-(1-BOC-2-(S)-azetidinylmethoxy)-5-bromo-6-chloropyridine

Product 1

HCID 98922203-(2-(S)-Azetidinylmethoxy)-6-chloro-5-(4-chlorophenyl)pyridineYield 124.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 3-(1-BOC-2-(S)-azetidinylmethoxy)-5-bromo-6-chloropyridine (650 mg, 1.73 mmol) and 4-chlorophenylboronic acid (284 mg, 1.82 mmol, Lancaster Chemical Co.) in toluene (10 mL) was added Pd(0) (37 mg) and Na2CO3 (5 mL of a 2 M solution), and the mixture was heated at reflux for 14 h. The solvent was removed under vacuum, and the residue was chromatographed (silica gel; EtOAc/hexane, 1:5 to 1:2) to afford the title compound (665 mg, 94 % yield): 1H NMR (CDCl3, 300 MHz) δ1.41 (s, 9H), 2.23-2.44 (m, 2H), 3.89 (t, J=7.5, Hz, 2H), 4.08-4.18 (m, 2H), 4.37 (m, 1H), 4.53 (m, 1H), 7.25 (d, J=3.0 Hz, 1H), 7.37-7.46 (m, 4H), 8.13 (d, J=3.0 Hz, 1H); MS (CI/NH3) m/z 409 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 14 h
  3. customThe solvent was removed under vacuum
  4. customthe residue was chromatographed (silica gel; EtOAc/hexane, 1:5 to 1:2)

Sources & evidence

ORD record
ord-44cdf9dc27d34ad89b823c9d34ed01dd
Source dataset
uspto-grants-2000_10
Patent number
US06127386

Reaction notes

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