Imidazole → tert-butyl 4-{2-[(1S)-1-hydroxypropyl]-4,5-dimethylphenyl}-3,6-dihydropyridine-1(2H)-carboxylate

HRID 29727Notes

Reaction equation

HRID 29727 reaction equation
[OH:1][C@@H:2]([C:5]1[CH:10]=[C:9]([CH3:11])[C:8]([CH3:12])=[CH:7][C:6]=1[C:13]1[CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:17][CH:18]=1)[CH2:3][CH3:4].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1C=CN=C1>C(Cl)Cl.[Zn](N=[N+]=[N-])N=[N+]=[N-]>[OH:1][C@H:2]([C:5]1[CH:10]=[C:9]([CH3:11])[C:8]([CH3:12])=[CH:7][C:6]=1[C:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:23])([CH3:25])[CH3:24])=[O:20])[CH2:15][CH:14]=1)[CH2:3][CH3:4]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 11776TriphenylphosphineHCID 58660096HCID 58660096, compound

Product 1

HCID 69208444tert-butyl 4-{2-[(1S)-1-hydroxypropyl]-4,5-dimethylphenyl}-3,6-dihydropyridine-1(2H)-carboxylate

Reagents, catalysts & solvents 2

HCID 178514646Zinc azideCatalystHCID 6344DichloromethaneSolvent

Procedure

Diisopropylazidocarboxylate (2.96 mL, 15.1 mmol) was added dropwise to a stirred mixture of alcohol 109 (1.3 g, 3.76 mmol), Zn(N3)2.2Py (prepared according to the method described by Viaud, M-C; Rollin, P. in Synthesis, 1990,130), triphenylphosphine (3.95 g, 15.1 mmol) and imidazole (1.03 g, 15.1 mmol) in DCM (100 mL) at approximately 0° C. After the addition, the resulting mixture was allowed to warm to ambient temperature and stirred vigorously for 18 h. The reaction mixture was filtered through a short column of silica gel eluted with the appropriate volume of DCM to remove excess salts and polar byproducts. The filtrate was concentrated in vacuo and the crude residue purified by flash chromatography on silica gel (gradient elution; 0%-20% EtOAc/hexanes as eluent) to afford azide 110 as a colorless oil.

Workup

  1. custom2Py (prepared
  2. additionAfter the addition
  3. filtrationThe reaction mixture was filtered through a short column of silica gel
  4. washeluted with the appropriate volume of DCM
  5. customto remove excess salts and polar byproducts
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe crude residue purified by flash chromatography on silica gel (gradient elution; 0%-20% EtOAc/hexanes as eluent)

Sources & evidence

ORD record
ord-615c0bb89fa34ca683928352e7c73563
Source dataset
uspto-grants-2008_09
Patent number
US07419990B2

Reaction notes

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