Triethylamine → 3-[(r)-2-(4-Benzyl-phenoxymethyl)-pyrrolidin-1-yl]-propionic acid methyl ester

HRID 1909614Notes

Reaction equation

HRID 1909614 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.C(N(CC)CC)C.Br[CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32]>CN(C=O)C>[CH3:34][O:33][C:31](=[O:32])[CH2:30][CH2:29][N:15]1[CH2:16][CH2:17][CH2:18][C@@H:14]1[CH2:13][O:12][C:11]1[CH:19]=[CH:20][C:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 76934Methyl 3-bromopropanoateHCID 16222640(2r)-2-[(4-Benzylphenoxy)methyl]pyrrolidine

Product 1

HCID 426417203-[(r)-2-(4-Benzyl-phenoxymethyl)-pyrrolidin-1-yl]-propionic acid methyl esterYield 13.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of Example 1 (0.2 g, 0.66 mmol) in DMF (5 mL) was added triethylamine (0.16 mL, 1.14 mmol) and methyl 3-bromopropionate (0.07 mL, 0.64 mmol). The resulting slurry was stirred at ambient temperature overnight. The solvent was removed under reduced pressure and the crude residue was extracted into ethyl acetate. The organic portion was washed with water, washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude product was purified by silica gel flash chromatography using hexane/EtOAc (gradient system) to give the title compound (0.03 g, 13%); 1H NMR (400 MHz, CDCl3); δ 1.68-1.80 (m, 3H), 1.93-2.04 (m, 1H), 2.29 (q, J=8.4 Hz, 1H), 2.53 (t, J=7.2 Hz, 2H), 2.70 (m, 1H), 2.87 (m, 1H), 3.13 (m, 1H), 3.24 (m, 1H), 3.66 (s, 3H), 3.75 (m, 1H), 3.92 (s, 2H), 3.93 (m, 1H), 6.82 (d, J=8.8 Hz, 2H), 7.08 (d, J=8.4 Hz, 2H), 7.16-7.20 (m, 3H), 7.27 (m, 2H); MS (m/z) 354.2 (M+1); LC (100.0%).

Workup

  1. customThe solvent was removed under reduced pressure
  2. extractionthe crude residue was extracted into ethyl acetate
  3. washThe organic portion was washed with water
  4. washwashed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-9ecf5a3d90e94dc08935b3c69e3ef8d2
Source dataset
uspto-grants-2013_12
Patent number
US08598359B2

Reaction notes

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