Triethylamine → 4-[(r)-2-(4-Benzyl-phenoxymethyl)-pyrrolidin-1-ylmethyl]-pyridine

HRID 1909613Notes

Reaction equation

HRID 1909613 reaction equation
[CH2:1]([C:8]1[CH:20]=[CH:19][C:11]([O:12][CH2:13][C@H:14]2[CH2:18][CH2:17][CH2:16][NH:15]2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[N:22]1[CH:27]=[CH:26][C:25]([CH2:28]Cl)=[CH:24][CH:23]=1.C(N(CC)CC)C>ClCCl>[CH2:1]([C:8]1[CH:20]=[CH:19][C:11]([O:12][CH2:13][C@H:14]2[CH2:18][CH2:17][CH2:16][N:15]2[CH2:28][C:25]2[CH:26]=[CH:27][N:22]=[CH:23][CH:24]=2)=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 745704-(Chloromethyl)pyridinium chlorideHCID 16222640(2r)-2-[(4-Benzylphenoxy)methyl]pyrrolidine

Product 1

HCID 162226434-[(r)-2-(4-Benzyl-phenoxymethyl)-pyrrolidin-1-ylmethyl]-pyridineYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of Example 1 (0.25 g, 0.82 mmol) in dichloromethane (2 mL) was added 4-picolyl chloride hydrochloride (0.13 g, 0.79 mmol) and triethylamine (0.29 mL, 2.08 mmol). The resulting mixture was stirred at ambient temperature overnight. The crude product was extracted into dichloromethane and washed with water followed by brine. The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography using hexane/EtOAc (gradient system) to give the title compound (0.11 g, 45%); 1H NMR (400 MHz, CDCl3); δ 1.70-1.81 (m, 3H), 2.03 (m, 1H), 2.27 (m, 1H), 2.94-3.03 (m, 2H), 3.49 (d, J=14.4 Hz, 1H), 3.86 (m, 1H), 3.92 (s, 2H), 3.94 (m, 1H), 4.19 (d, J=14.4 Hz, 1H), 6.79 (d, J=8.8 Hz, 2H), 7.08 (d, J=8.8 Hz, 2H), 7.15-7.20 (m, 3H), 7.26-7.29 (m, 4H), 8.51 (m, 2H); MS (m/z) 359.5 (M+1); LC (99.7%); HPLC (91.6%)

Workup

  1. extractionThe crude product was extracted into dichloromethane
  2. washwashed with water
  3. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-b4aa4112c5094a5a8a77dd9f0c0536cb
Source dataset
uspto-grants-2013_12
Patent number
US08598359B2

Reaction notes

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