Imidazole → HCID 21186607, compound

HRID 1384320Notes

Reaction equation

HRID 1384320 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([CH3:13])[C:11]=1[OH:12])[O:8][CH2:7][CH2:6][C:5]2=[O:14].N1C=CN=C1.[CH:20]([Si:23](Cl)([CH:27]([CH3:29])[CH3:28])[CH:24]([CH3:26])[CH3:25])([CH3:22])[CH3:21]>CN(C)C=O.O>[CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([CH3:13])[C:11]=1[O:12][Si:23]([CH:27]([CH3:29])[CH3:28])([CH:24]([CH3:26])[CH3:25])[CH:20]([CH3:22])[CH3:21])[O:8][CH2:7][CH2:6][C:5]2=[O:14]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 139400Triisopropylsilyl chlorideHCID 21186587HCID 21186587, compound

Product 1

HCID 21186607HCID 21186607, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 6,8-dimethyl-7-hydroxychroman-4-one (the compound of Preparation 26, 0.50 g, 2.60 mmol), imidazole (0.35 g, 5.14 mmol), and triisopropylsilyl chloride (0.61 mL, 2.85 mmol) in dimethylformamide (10 mL) was stirred at ambient temperature overnight. The reaction was diluted with water and extracted with ether (2x). The combined organic phase was washed with 1N lithium chloride (2x) and brine, dried over magnesium sulfate and concentrated. The residue was flash chromatographed on silica gel (1×4 inches packed in hexane) with elution proceeding as follows: 5% ethyl acetate/hexane (100 mL), nil; 5% ethyl acetate/hexane (100 mL) and 10% ethyl acetate/hexane (150 mL), 0.529 g (58%) of 6,8-dimethyl-7-triisopropylsilyloxychroman-4-one as a waxy lemon yellow solid which had: NMR δ7.57 (s, 1 H), 4.52 (t, J=6.4 Hz, 2 H), 2.74 (t, J=6.4 Hz, 2 H), 2.21 (s, 3 H), 2.11 (s, 3 H), 1.40-1.26 (m, 3 H), 1.13 (d, J=7.2 Hz, 18 H); 13C NMR δ191.60, 160.25, 159.93, 125.91, 122.55, 116.15, 115.29, 67.24, 37.52, 17.91, 17.69, 17.38, 14.24, 12.28, 9.97. A small silyl impurity was noted in the proton NMR at 1.06 ppm however, the material was found to be suitable for further transformations without additional purification.

Workup

  1. extractionextracted with ether (2x)
  2. washThe combined organic phase was washed with 1N lithium chloride (2x) and brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customchromatographed on silica gel (1×4 inches packed in hexane) with elution proceeding
  6. customto be suitable for further transformations without additional purification

Sources & evidence

ORD record
ord-1f69772d67c4441f82b7bb68816c50af
Source dataset
uspto-grants-2001_07
Patent number
US06258827B1

Reaction notes

Loading…