Water → 3,5-Bis(trifluoromethyl)-alpha-{[2-(trimethylsilyl)ethoxy]methoxymethyl}benzenemethanol

HRID 966967Notes

Reaction equation

HRID 966967 reaction equation
C(N(C(C)C)C(C)C)C.[F:10][C:11]([F:27])([F:26])[C:12]1[CH:13]=[C:14]([CH:22]([OH:25])[CH2:23][OH:24])[CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:17]=1.Cl[CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34].O>ClCCl>[F:10][C:11]([F:26])([F:27])[C:12]1[CH:13]=[C:14]([CH:22]([CH2:23][O:24][CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[OH:25])[CH:15]=[C:16]([C:18]([F:20])([F:21])[F:19])[CH:17]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 222935121-[3,5-Bis(trifluoromethyl)phenyl]ethane-1,2-diol

Product 1

HCID 865903613,5-Bis(trifluoromethyl)-alpha-{[2-(trimethylsilyl)ethoxy]methoxymethyl}benzenemethanolYield 49%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N-Ethyl-N,N-diisopropylamine (465 μl, 2.67 mmol) was added over 2 minutes, to a solution of (RS)-1-[3,5-bis(trifluoromethyl)phenyl]-1,2-ethanediol (Description 3, 488 mg, 1.78 mmol) and [2-(chloromethoxy)ethyl]trimethylsilane (315 μl, 1.78 mmol) in dichloromethane (3 mL) and the mixture was stirred at room temperature for 4 hours, then at 50° C. for 1 hour. The mixture was cooled and dichloromethane (20 mL) and water (20 mL) were added. The layers were separated and the aqueous layer was extracted with dichloromethane (10 mL). The combined organic fractions were dried (Na2SO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with isohexane/EtOAc (90:10) to give the title compound (352 mg, 49%). 1H NMR (400 MHz, CDCl3) δ 7.86 (2H, s), 7.79 (1H, s), 4.96 (1H, m), 4.73 (2H, s), 3.87 (1H, dd, J 11.1, 3.0 Hz), 3.73 (1H, br s), 3.61 (3H, m), 0.93 (2H, t, J 8.5 Hz), and 0.02 (9H, s).

Workup

  1. waitat 50° C. for 1 hour
  2. temperatureThe mixture was cooled
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with dichloromethane (10 mL)
  5. dry with materialThe combined organic fractions were dried (Na2SO4)
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel
  8. washeluting with isohexane/EtOAc (90:10)

Sources & evidence

ORD record
ord-26ef180a91d445458ac6694f42f4c006
Source dataset
uspto-grants-2005_10
Patent number
US06953792B2

Reaction notes

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