Imidazole → HCID 23525647, compound

HRID 644952Notes

Reaction equation

HRID 644952 reaction equation
[N:1](C(OCC)=O)=[N:2]C(OCC)=O.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH2:21][CH2:22][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:24][CH:25]=2)=[C:16]([C@H:33](O)[CH3:34])[CH:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH:55]1C=CN=C1>ClCCl.[Zn](N=[N+]=[N-])N=[N+]=[N-]>[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH2:21][CH2:22][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:24][CH:25]=2)=[C:16]([C@@H:33]([N:55]=[N+:1]=[N-:2])[CH3:34])[CH:15]=1

Participants

7

Reactant 4

HCID 795ImidazoleHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 68519018Tert-Butyl 4-{4-Chloro-2-[(1R)-1-Hydroxyethyl]Phenyl}-3,6-Dihydropyridine-1(2H)-Carboxylate

Product 1

HCID 23525647HCID 23525647, compound

Reagents, catalysts & solvents 2

HCID 178514646Zinc azideCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of diethyl azodicarboxylate (49.6 mL, 0.315 mol) was added dropwise to a stirred mixture of tert-butyl 4-{4-chloro-2-[(1R)-1-hydroxyethyl]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate (26.7 g, 78.9 mmol), Zn(N3)2.2Py (prepared according to: Viaud, M-C; Rollin, P. Synthesis 1990:130-131) (48.5 g, 0.158 mol), triphenylphosphine (82.7 g, 0.315 mol) and imidazole (21.5 g, 0.315 mol) in dichloromethane at approximately 0° C. After the addition, the resulting mixture was allowed to warm to ambient temperature and stirred vigorously for 3 days. The reaction mixture was filtered through a short column of silica gel eluted with the appropriate volume of dichloromethane to remove excess salts and polar byproducts. The filtrate was concentrated in vacuo and the crude residue was purified by flash chromatography on silica gel (12.5% ethyl acetate/hexanes as eluent) to furnish the title compound as a viscous pale yellow oil.

Workup

  1. additionAfter the addition
  2. filtrationThe reaction mixture was filtered through a short column of silica gel
  3. washeluted with the appropriate volume of dichloromethane
  4. customto remove excess salts and polar byproducts
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe crude residue was purified by flash chromatography on silica gel (12.5% ethyl acetate/hexanes as eluent)

Sources & evidence

ORD record
ord-9817cd2b1e83400ea35ce1dd8e1b184e
Source dataset
uspto-grants-2010_04
Patent number
US07700778B2

Reaction notes

Loading…