1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-2-(4-Fluoro-3,5-dimethyl-phenylamino)-hexanoic acid tert-butoxy-amide

HRID 885502Notes

Reaction equation

HRID 885502 reaction equation
[F:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([NH:9][C@H:10]([CH2:14][CH2:15][CH2:16][CH3:17])[C:11]([OH:13])=O)=[CH:4][C:3]=1[CH3:18].[C:19]([O:23][NH2:24])([CH3:22])([CH3:21])[CH3:20].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>[C:19]([O:23][NH:24][C:11](=[O:13])[C@H:10]([NH:9][C:5]1[CH:4]=[C:3]([CH3:18])[C:2]([F:1])=[C:7]([CH3:8])[CH:6]=1)[CH2:14][CH2:15][CH2:16][CH3:17])([CH3:22])([CH3:21])[CH3:20]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 61063N-MethylmorphineHCID 757711-HydroxybenzotriazoleHCID 2777907O-tert-butylhydroxylamineHCID 69189506(R)-2-(4-Fluoro-3,5-dimethyl-phenylamino)-hexanoic acid

Product 1

HCID 86667068(R)-2-(4-Fluoro-3,5-dimethyl-phenylamino)-hexanoic acid tert-butoxy-amideYield 38.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of crude (R)-2-(4-fluoro-3,5-dimethyl-phenylamino)-hexanoic acid (ca. 6.0 mmol), O-tert-butyl-hydroxyamine (2.261 g, 18.0 mmol), HOBT (0.811 g, 6.0 mmol), and N-methyl morphine (3.036 g, 30.0 mmol) in 20 mL of dichloromethane, was added EDCI (1.725 g, 9.0 mmol). After stirring at room temperature under N2 for 44 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 and the solvents removed under reduced pressure. The product was isolated by Flash chromatography (silica gel) eluting with 0-30% ethyl acetate/hexanes to give the title compound as a pale yellow semi-solid (0.747 g, 38% yield). LC-MS: tR=8.8 min; m/z 325 (M+H)+.

Workup

  1. extractionextracted with dichloromethane (60 mL×3)
  2. dry with materialdried over anhydrous Na2SO4
  3. customthe solvents removed under reduced pressure
  4. customThe product was isolated by Flash chromatography (silica gel)
  5. washeluting with 0-30% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-1ff177eb7e8149a3a056da007a31c06c
Source dataset
uspto-grants-2012_08
Patent number
US08242174B2

Reaction notes

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