1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-(4-Fluoro-3-methyl-benzyl)-hexanoic acid (tetrahydro-pyran-2-yloxy)-amide

HRID 1158124Notes

Reaction equation

HRID 1158124 reaction equation
[F:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][CH:7]([CH2:11][CH2:12][CH2:13][CH3:14])[C:8]([OH:10])=O)=[CH:4][C:3]=1[CH3:17].[O:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]1[O:24][NH2:25].C1C=CC2N(O)N=NC=2C=1.C[N+]1(C)[C@H]2CC3C=CC(O)=C4O[C@H]5[C@@H](O)C=C[C@@H]2[C@]5(C=34)CC1.CCN=C=NCCCN(C)C>ClCCl.O>[O:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]1[O:24][NH:25][C:8](=[O:10])[CH:7]([CH2:6][C:5]1[CH:15]=[CH:16][C:2]([F:1])=[C:3]([CH3:17])[CH:4]=1)[CH2:11][CH2:12][CH2:13][CH3:14]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 61063N-MethylmorphineHCID 757711-HydroxybenzotriazoleHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 595125992-(4-Fluoro-3-methyl-benzyl)-hexanoic acid

Product 1

HCID 595125952-(4-Fluoro-3-methyl-benzyl)-hexanoic acid (tetrahydro-pyran-2-yloxy)-amideYield 60%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(4-Fluoro-3-methyl-benzyl)-hexanoic acid (0.498 g, 2.091 mmol), O-(tetrahydro-pyran-2-yl)-hydroxylamine (0.735 g, 6.274 mmol), HOBT (0.282 g, 2.091 mmol), and N-methyl morphine (1.058 g, 10.455 mmol) in 20 mL of dichloromethane, was added EDCI (0.601 g, 3.137 mmol). After stirring at room temperature under N2 for 64 h, the reaction mixture was diluted with 60 mL of water and extracted with dichloromethane (60 mL×3). The organic extracts were combined and dried over anhydrous Na2SO4. After removing the solvents under reduced pressure, the product was isolated by Flash chromatography (silica gel) eluting with 0-40% ethyl acetate/hexanes to give the title compound as a pale yellow solid (0.423 g, 60% yield). LC-MS: tR=9.1 min; m/z 338 (M+H)+.

Workup

  1. extractionextracted with dichloromethane (60 mL×3)
  2. dry with materialdried over anhydrous Na2SO4
  3. customAfter removing the solvents under reduced pressure
  4. customthe product was isolated by Flash chromatography (silica gel)
  5. washeluting with 0-40% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-5a64fc5584e641d3af056664a5ca161b
Source dataset
uspto-grants-2010_10
Patent number
US07807720B2

Reaction notes

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