Triethylamine → HCID 69741938, compound

HRID 1760373Notes

Reaction equation

HRID 1760373 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:10][CH2:9][C:8](=[O:11])[N:7]1[C:12]1[CH:13]=[N:14][C:15]([O:18][C:19]2[CH:24]=[CH:23][C:22]([CH2:25]O)=[CH:21][CH:20]=2)=[CH:16][CH:17]=1)=[O:5])[CH3:2].C(N(CC)CC)C.CS(Cl)(=O)=O.[Br-:44].[Li+]>C(Cl)Cl.O1CCCC1.C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C:6]1([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:10][CH2:9][C:8](=[O:11])[N:7]1[C:12]1[CH:13]=[N:14][C:15]([O:18][C:19]2[CH:24]=[CH:23][C:22]([CH2:25][Br:44])=[CH:21][CH:20]=2)=[CH:16][CH:17]=1)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 8471Triethylamine2×HCID 31297Methanesulfonyl chloride2×HCID 82050Lithium BromideHCID 69742791HCID 69742791, compound

Product 1

HCID 69741938HCID 69741938, compoundYield 69.6%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-40 °C

Procedure

To a solution of 1-[6-(4-hydroxymethyl-phenoxy)-pyridin-3-yl]-5-oxo-pyrrolidine-2,2-dicarboxylic acid diethyl ester (0.80 g, 1.9 mmol) in 9.4 mL of methylene chloride was added triethylamine (0.46 mL, 0.33 g, 3.3 mL). After cooling to −40° C., the mixture was treated with methanesulfonyl chloride (0.20 mL, 0.30 g, 2.61 mmol). After stirring for 1 hour, an additional 0.10 mL of methanesulfonyl chloride and 0.4 mL of triethylamine were added, and stirring was continued for 1 hour. A solution of anhydrous lithium bromide (1.6 g, 19 mmol, flame dried under vacuum before use) in tetrahydrofuran (20 mL) was added via cannula, and the mixture was warmed to room temperature and stirred for 2 hours. The mixture was diluted with ethyl acetate, and the organic phase was washed with water, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was filtered through a pad of silica gel eluting with 1:1 ethyl acetate-hexanes, affording 0.65 g of 1-[6-(4-bromomethyl-phenoxy)-pyridin-3-yl]-5-oxo-pyrrolidine-2,2-dicarboxylic acid diethyl ester as a colorless syrup. 1H NMR (CDCl3, 500 MHz): 8.07 (d, 1H, J=3.0 Hz), 7.76 (dd, 1H, J=2.5, 8.5 Hz), 7.44 (d, 2H, J=8.5 Hz), 7.12 (d, 2H, J=8.0 Hz), 6.95 (d, 1H, J=9.0 Hz), 4.53 (s, 2H), 4.22 (q, 4H, J=7.0 Hz), 2.75 (m, 2H), 1.20 (t, 6H, J=7.0 Hz) ppm.

Workup

  1. stirringstirring
  2. waitwas continued for 1 hour
  3. temperaturethe mixture was warmed to room temperature
  4. stirringstirred for 2 hours
  5. washthe organic phase was washed with water
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. filtrationThe residue was filtered through a pad of silica gel eluting with 1:1 ethyl acetate-hexanes

Sources & evidence

ORD record
ord-9ce8d2a545034192bb07e24fc9e480d8
Source dataset
uspto-grants-2005_01
Patent number
US06841671B2

Reaction notes

Loading…