Imidazole → 4'-(6-((Tert-butyldimethylsilyl)oxy)hexyloxy)-4-biphenylcarboxylic acid

HRID 890904Notes

Reaction equation

HRID 890904 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([OH:23])=[O:22])=[CH:17][CH:16]=2)=[CH:11][CH:10]=1.[Si:24](Cl)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25].N1C=CN=C1.C([O-])([O-])=O.[K+].[K+]>CN(C)C=O.O1CCCC1.CO.O.C(OCC)C>[Si:24]([O:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]([C:21]([OH:23])=[O:22])=[CH:19][CH:20]=2)=[CH:11][CH:10]=1)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25]

Participants

10

Reactant 4

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 28928tert-Butyldimethylsilyl chlorideHCID 222424974-(6-Hydroxyhexyloxy)biphenyl-4'-carboxylic acid

Product 1

HCID 222424914'-(6-((Tert-butyldimethylsilyl)oxy)hexyloxy)-4-biphenylcarboxylic acidYield 99.5%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 9 (12.0 g, 38.22 mmol) and tert-butyldimethylsilyl chloride (13.07 g, 86.68 mmol) in anhydrous N,N-dimethylformamide (80 mL) was quickly added imidazole (10.62 g, 155.96 mmol). After stirring under argon overnight, the reaction mixture was shaken with diethyl ether (100 mL) and water (300 mL). The ethereal layer was separated and washed with a saturated NaHCO3 solution before drying over anhydrous MgSO4. The crude product resulting from evaporation of the solvent was purified by flash column chromatography on silica gel with methylene chloride: hexanes (1:1) as the eluent to afford a compound with silyl-protected hydroxyl and carboxyl groups. The compound was dissolved in tetrahydrofuran:methanol (120 mL:60 mL) followed by stirring with a solution of 10% K2CO3 aqueous solution (60 mL) for 1 h. The volume of the solution was reduced to 25% via evaporation under reduced pressure. Brine (250 ml; 120 g NaCl in 500 mL H2O) was added to the slurry, and the pH was adjusted to 5.0 with 1 M aqueous solution of potassium hydrogen sulfate, KHSO4. The precipitate was collected by filtration and washed with water followed by drying under vacuum at 70° C. to yield 10 (16.3 g, 99%). 1H NMR spectral data (400 MHz, Acetone-d6): δ 0.03 (s, 6H, —Si(CH3)2), δ 0.86 (s, 9H, —SiCCH3), δ 1.30–1.60 (m, 6H, —CH2—), δ 1.74 (m, 2H, —CH2—), δ 3.59 (t, 2H, —CH2OAr), δ 4.01 (t, 2H, SiOCH2—), δ7.03 (d, 2H, aromatic rings), δ 7.66 (d, 2H, aromatic rings), δ 7.70 (d, 2H, aromatic rings), δ 7.97 (d, 2H, aromatic rings).

Workup

  1. customThe ethereal layer was separated
  2. washwashed with a saturated NaHCO3 solution
  3. dry with materialbefore drying over anhydrous MgSO4
  4. customThe crude product resulting from evaporation of the solvent
  5. customwas purified by flash column chromatography on silica gel with methylene chloride: hexanes (1:1) as the eluent
  6. customto afford a compound with silyl-protected hydroxyl and carboxyl groups
  7. customThe volume of the solution was reduced to 25% via evaporation under reduced pressure
  8. additionBrine (250 ml; 120 g NaCl in 500 mL H2O) was added to the slurry
  9. filtrationThe precipitate was collected by filtration
  10. washwashed with water
  11. customby drying under vacuum at 70° C.

Sources & evidence

ORD record
ord-c850d5ceb8d6436d824b3ba5e5a81751
Source dataset
uspto-grants-2006_02
Patent number
US07001648B2

Reaction notes

Loading…