Water → 4-[5-(2-Hydroxyethyl)-imidazol-1-yl]-3,3-dimethyl-isochroman-1-one

HRID 1690750Notes

Reaction equation

HRID 1690750 reaction equation
[Si]([O:8][CH2:9][CH2:10][C:11]1[N:15]([CH:16]([C:21]2[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=2[C:23]#N)[C:17]([OH:20])([CH3:19])[CH3:18])[CH:14]=[N:13][CH:12]=1)(C(C)(C)C)(C)C.S(=O)(=O)(O)[OH:30].O.[OH-].[Na+]>C1COCC1>[OH:8][CH2:9][CH2:10][C:11]1[N:15]([CH:16]2[C:21]3[C:22](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:23](=[O:30])[O:20][C:17]2([CH3:19])[CH3:18])[CH:14]=[N:13][CH:12]=1

Participants

6

Reactant 4

HCID 962WaterHCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 577810882-(1-{5-[2-(Tert-butyldimethylsilanyloxy)-ethyl]-imidazol-1-yl}-2-hydroxy-2-methyl-propyl)-benzonitrile

Product 1

HCID 577811284-[5-(2-Hydroxyethyl)-imidazol-1-yl]-3,3-dimethyl-isochroman-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-(1-{5-[2-(tert-Butyldimethylsilanyloxy)-ethyl]-imidazol-1-yl}-2-hydroxy-2-methyl-propyl)-benzonitrile (1.5 g, 3.75 mmol) is dissolved in THF (15 mL). Concentrated sulfuric acid (0.80 mL, 15.03 mmol) and water (0.80 mL) are added and the mixture is stirred at reflux for 24 h. After cooling down, the mixture is basified to pH 10 using 10% aqueous sodium hydroxide and is then 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 4-[5-(2-hydroxy-ethyl)-imidazol-1-yl]-3,3-dimethyl-isochroman-1-one; HRMS (ESI) m/z 287.1403; [(M+H)+ Calcd for C16H19N2O3: 287.1396]; 1H NMR (400 MHz, MeOD) δ ppm 1.26 (s, 3 H), 1.56 (s, 3 H), 3.06 (br. s, 2 H), 3.75-4.18 (m, 2 H), 5.74 (br. s, 1 H), 6.92 (br. s, 1 H), 7.15 (d, J=1.3 Hz, 1 H), 7.57 (d, J=7.3 Hz, 1 H), 7.67 (t, J=7.3 Hz, 1 H), 7.78 (t, J=7.3 Hz, 1 H), 8.24 (d, J=7.3 Hz, 1 H)

Workup

  1. temperatureat reflux for 24 h
  2. temperatureAfter cooling down
  3. extractionis then extracted 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-020e0e326a3545cf9a31d45cc3cd2b5c
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

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