Imidazole → 4-(3-{[tert-Butyl(dimethyl)silyl]oxy}propoxy)benzoic acid

HRID 890900Notes

Reaction equation

HRID 890900 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:14]=[CH:13][C:9]([C:10]([OH:12])=[O:11])=[CH:8][CH:7]=1.[Si:15](Cl)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16].N1C=CN=C1.C([O-])([O-])=O.[K+].[K+]>CN(C)C=O.O1CCCC1.O.CO.C(OCC)C>[Si:15]([O:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:14]=[CH:13][C:9]([C:10]([OH:12])=[O:11])=[CH:8][CH:7]=1)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]

Participants

10

Reactant 4

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 28928tert-Butyldimethylsilyl chlorideHCID 134232864-(3-Hydroxypropoxy)benzoic acid

Product 1

HCID 222424964-(3-{[tert-Butyl(dimethyl)silyl]oxy}propoxy)benzoic acidYield 88,255.898%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1 (10.0 g, 0.05 mmol) and tert-butyldimethylsilyl chloride (17.50 g, 0.11 mmol 1) in anhydrous N,N-dimethylformamide (45 mL) was quickly added imidazole (14.16 g, 0.21 mmol) under argon. After stirring overnight, the reaction mixture was shaken with diethyl ether (100 mL) and water (300 mL). The ether layer was separated and washed with a saturated NaHCO3 solution (100 mL×2) before drying over anhydrous MgSO4. The solvent was evaporated, and the solid residue was purified by flash column chromatography on silica gel with methylene chloride: hexanes (1:1) as the eluent to afford 2 with silyl-protected hydroxyl and carboxyl groups. This compound was dissolved in tetrahydrofuran: methanol (50 mL: 150 mL) followed by stirring with a solution of K2CO3 (5 g, 36.18 mmol) in water (50 mL) for 1 h. The volume of the solution was reduced by 75% via evaporation under reduced pressure. Brine (150 mL; 120 g NaCl in 500 mL H2O) was added to the resultant slurry, and the pH was adjusted to 5.0 with a 1 M KHSO4 solution. The precipitate was collected by filtration and washed with water before drying under vacuum at 60° C. to yield 2 (13.7 g, 87%). 1H NMR (200 MHz, CDCl3): δ 0.06 (s, 6H, —S1—CH3), δ 0.91 (s, 9H,-SiCCH3)δ 2.01 (quintet, 2H, —CH2—), δ 3.81 (t, 2H, —CH2OAr), δ 4.16 (t, 2 H, HOCH2—), δ 6.96 (d, 2H, aromatic ring), δ 8.06 (d, 2H, aromatic ring).

Workup

  1. customThe ether layer was separated
  2. washwashed with a saturated NaHCO3 solution (100 mL×2)
  3. dry with materialbefore drying over anhydrous MgSO4
  4. customThe solvent was evaporated
  5. customthe solid residue was purified by flash column chromatography on silica gel with methylene chloride: hexanes (1:1) as the eluent
  6. customto afford 2 with silyl-protected hydroxyl and carboxyl groups
  7. customThe volume of the solution was reduced by 75% via evaporation under reduced pressure
  8. additionBrine (150 mL; 120 g NaCl in 500 mL H2O) was added to the resultant slurry
  9. filtrationThe precipitate was collected by filtration
  10. washwashed with water
  11. custombefore drying under vacuum at 60° C.

Sources & evidence

ORD record
ord-da74672efe0142a5bde0802fa59a004f
Source dataset
uspto-grants-2006_02
Patent number
US07001648B2

Reaction notes

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