Sodium Carbonate → 3-(1-Boc-2-(r)-pyrrolidinylmethoxy)-5-(4-chlorophenyl)pyridine

HRID 365863Notes

Reaction equation

HRID 365863 reaction equation
[C:1]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][O:14][C:15]1[CH:16]=[N:17][CH:18]=[C:19](Br)[CH:20]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[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>[C:1]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:16]=[N:17][CH:18]=[C:19]([C:26]2[CH:27]=[CH:28][C:23]([Cl:22])=[CH:24][CH:25]=2)[CH:20]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 15480235(S)-2-((5-Bromopyridin-3-yloxy)methyl)pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 229618123-(1-Boc-2-(r)-pyrrolidinylmethoxy)-5-(4-chlorophenyl)pyridineYield 120.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 3-(1-BOC-2-(S)-pyrrolidinylmethoxy)-5-bromopyridine (280 mg, 0.79 mmol) and 4-chlorophenylboronic acid (246 mg, 1.57 mmol, Lancaster Chemical Co.) in toluene (10 mL) was added Pd(0) (30 mg) and Na2CO3 (2.5 mL of a 2 M solution), and the mixture was heated at reflux for 6 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 (370 mg, >100% yield): 1H NMR (CDCl3, 300 MHz) δ1.47 (s, 9H), 1.80-2.10 (m, 3H), 3..30-3.49 (m, 2H), 3.90-4.30 (m, 3H), 7.40-7.60 (m, 5H), 8.31 (s, 1H), 8.42 (s, 1H); MS (CI/NH3) m/z 389 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 6 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-73a7101b863f488688a1e44e5cfd7644
Source dataset
uspto-grants-2000_10
Patent number
US06127386

Reaction notes

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