Imidazole → HCID 67006120, compound

HRID 564345Notes

Reaction equation

HRID 564345 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH:11]2[C:20]3[C:15](=[C:16]([F:22])[CH:17]=[CH:18][C:19]=3[F:21])[O:14][CH2:13][CH:12]2[CH2:23][CH2:24][CH:25]([OH:29])[CH2:26][CH:27]=[CH2:28])(=[O:10])=[O:9])=[CH:4][CH:3]=1.N1C=CN=C1.[CH3:35][C:36]([Si:39](Cl)([CH3:41])[CH3:40])([CH3:38])[CH3:37]>CN(C=O)C>[C:36]([Si:39]([O:29][CH:25]([CH2:24][CH2:23][CH:12]1[CH:11]([S:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)(=[O:9])=[O:10])[C:20]2[C:15](=[C:16]([F:22])[CH:17]=[CH:18][C:19]=2[F:21])[O:14][CH2:13]1)[CH2:26][CH:27]=[CH2:28])([CH3:41])[CH3:40])([CH3:38])([CH3:37])[CH3:35]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 67006420HCID 67006420, compound

Product 1

HCID 67006120HCID 67006120, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 1-[4-(4-chloro-benzenesulfonyl)-5,8-difluoro-chroman-3-yl]-hex-5-en-3-ol (1.30 g, 2.93 mmol) in DMF (29 mL) 0° C. was treated with imidazole (0.41 g, 6.0 mmol), TBSCl (0.66 g, 4.4 mmol) and warmed to ambient temperature. After 36 h, the reaction mixture was quenched with saturated aqueous NH4Cl and extracted with EtOAc (2×). The combined organic extracts were washed H2O (3×), saturated aqueous NaHCO3, brine, dried over MgSO4 and concentrated in vacuo. Flash chromatography (1→10% EtOAc/Hex) afforded the title compound (1.45 g, 89%): 1H NMR (CDCl3 400 MHz) δ 7.71 (dd, J=8.1, 1.5 Hz, 2H), 7.52 (dd, J=8.1, 1.5 Hz, 2H), 7.03 (m, 1H), 6.42 (m, 1H), 5.72 (m, 1H), 5.01-4.89 (m, 3H), 4.33 (dd, J=11.0, 2.2 Hz, 1H), 4.27 (s, 1H), 3.62 (m, 1H), 2.74 (m, 1H), 2.12-2.10 (m, 2H), 1.55-1.24 (m, 4H), 0.78 (s, 4.5H), 0.76 (s, 4.5H), −0.01 (s, 3H), −0.08 (s, 3H).

Workup

  1. customthe reaction mixture was quenched with saturated aqueous NH4Cl
  2. extractionextracted with EtOAc (2×)
  3. washThe combined organic extracts were washed H2O (3×), saturated aqueous NaHCO3, brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5d98cc55a04a41a0abf288c0add112e4
Source dataset
uspto-grants-2011_11
Patent number
US08067621B2

Reaction notes

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