Sulfuric Acid → HCID 57781149, compound

HRID 1690725Notes

Reaction equation

HRID 1690725 reaction equation
[Si]([O:8][CH2:9][C:10]1[N:14]([CH:15]([C:20]2[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[C:21]=2[C:22]#N)[C:16]([OH:19])([CH3:18])[CH3:17])[CH:13]=[N:12][CH:11]=1)(C(C)(C)C)(C)C.S(=O)(=O)(O)[OH:30].C(=O)(O)[O-].[Na+]>O1CCOCC1.O>[Cl:28][C:24]1[CH:25]=[CH:26][CH:27]=[C:20]2[C:21]=1[C:22](=[O:30])[O:19][C:16]([CH3:18])([CH3:17])[CH:15]2[N:14]1[C:10]([CH2:9][OH:8])=[CH:11][N:12]=[CH:13]1

Participants

6

Reactant 3

HCID 1118Sulfuric AcidHCID 516892Sodium BicarbonateHCID 66906494HCID 66906494, compound

Product 1

HCID 57781149HCID 57781149, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

2-{1-[5-(tert-Butyldimethylsilanyloxymethyl)-imidazol-1-yl]-2-hydroxy-2-methyl-propyl}-6-chloro-benzonitrile (0.188 g, 0.616 mmol), prepared in a similar fashion as described in Example 6c is dissolved in 1,4-dioxane (5 mL). Concentrated sulfuric acid (0.130 mL, 2.46 mmol) and water (0.130 mL) are added and the mixture is stirred at reflux for 16 h. After cooling down, the mixture is basified to pH 10 using solid sodium bicarbonate and is then diluted with water and extracted with ethyl acetate twice. The combined organic phase is dried over Na2SO4 and concentration in vacuo. The residue obtained is purified by silica gel chromatography (dichloromethane-methanol, 9:1) to give 8-chloro-4-(5-hydroxymethyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one; HRMS (ESI) m/z 307.0845 [(M+H)+: Calcd for C15H16N2O3Cl: 307.0849]; 1H NMR (400 MHz, MeOD) δ ppm 1.30 (s, 3 H), 1.56 (s, 3 H), 4.77 (d, J=13.6 Hz, 1 H), 4.83 (d, J=13.6 Hz, 1 H), 5.77 (s, 1 H), 7.02 (s, 1 H), 7.35 (s, 1 H), 7.55 (br. d, J=7.3 Hz, 1 H), 7.68 (dd, J=8.0, 7.3 Hz, 1 H), 7.72 (dd, J=8.0, 1.5 Hz, 1 H).

Workup

  1. temperatureat reflux for 16 h
  2. temperatureAfter cooling down
  3. extractionextracted with ethyl acetate twice
  4. dry with materialThe combined organic phase is dried over Na2SO4 and concentration in vacuo
  5. customThe residue obtained
  6. customis purified by silica gel chromatography (dichloromethane-methanol, 9:1)

Sources & evidence

ORD record
ord-897766d4078d4b3db0c5e6b09240d6fa
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

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