Sodium Carbonate → 5-(4-Chlorophenyl)-3-(2-(r)-pyrrolidinylmethoxy)pyridine

HRID 365815Notes

Reaction equation

HRID 365815 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2C(OC(C)(C)C)=O)[CH:5]=[N:6][CH:7]=1.[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>[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([C:2]2[CH:3]=[C:4]([O:8][CH2:9][C@H:10]3[CH2:14][CH2:13][CH2:12][NH:11]3)[CH:5]=[N:6][CH:7]=2)=[CH:25][CH:24]=1

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 541629085-(4-Chlorophenyl)-3-(2-(r)-pyrrolidinylmethoxy)pyridineYield 134%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 5-bromo-3-(1-BOC-2-(S)-pyrrolidinylmethoxy)pyridine (300 mg, 0.84 mmol) and 4-chlorophenylboronic acid (263 mg, 1.68 mmol, Lancaster Chemical Co.) in toluene (10 mL) was added Pd(0) (25 mg) and Na2CO3 (1 mL of a 2M solution), and the mixture was heated at reflux for 6 hours. The solvent was removed under vacuum, and the residue was chromatographed on a silica gel column, eluting with 1:5 to 1:2 EtOAc/hexane to afford the title compound (325 mg, 100% yield). MS (CI/NH3) m/z 389 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ: 1.47 (s, 9h), 1.90 (m, 2H), 2.05 (br, 1H), 3.40 (br, 2H), 3.92 (br, 1H), 4.19 (br, 2H), 4.25 (br, 1H), 7.44 (m, 2H), 7.52 (m, 3H), 8.31 (m, 1H), 8.42 (s, 1H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 6 hours
  3. customThe solvent was removed under vacuum
  4. customthe residue was chromatographed on a silica gel column
  5. washeluting with 1:5 to 1:2 EtOAc/hexane

Sources & evidence

ORD record
ord-15933877f310419fa0c3940ec091c264
Source dataset
uspto-grants-2000_10
Patent number
US06127386

Reaction notes

Loading…