4-Methoxybenzyl alcohol → (R)-1,1,1-Trifluoro-3-[(4-methoxybenzyl)oxy]-2-propanol

HRID 420317Notes

Reaction equation

HRID 420317 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:12]=[CH:11][C:8]([CH2:9][OH:10])=[CH:7][CH:6]=1.[CH2:13]1[O:15][C@H:14]1[C:16]([F:19])([F:18])[F:17]>C1COCC1.O>[F:17][C:16]([F:19])([F:18])[C@H:14]([OH:15])[CH2:13][O:10][CH2:9][C:8]1[CH:11]=[CH:12][C:5]([O:4][CH3:3])=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 77384-Methoxybenzyl alcoholHCID 24758Sodium hydrideHCID 7016923(2R)-2-(trifluoromethyl)oxirane

Product 1

HCID 66649618(R)-1,1,1-Trifluoro-3-[(4-methoxybenzyl)oxy]-2-propanol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of NaH (390 mg, 8.9 mmol, 55% in mineral oil) in THF (10 mL) at 0° C. was added 4-methoxybenzylalcohol (1.27 g, 8.92 mmol) in THF (5 mL). After 1 h stirring at 0° C. R-(+)-3,3,3-trifluoro-1,2-epoxypropane (500 mg, 4.46 mmol) was added to a 20 mL microwave vial via syringe. The closed vial was heated at 100° C. for 18 h. The reaction mixture was diluted with water and extracted twice with Et2O. The organic phase was washed with brine, dried over MgSO4, filtered and evaporated. Chromatography over silica (cyclohexane-EtOAc 95:5 to cyclohexane-EtOAc 75:25) afforded the title compound: ESIMS [M+NH4]+=268; 1H NMR (360 MHz, CDCl3): δ 7.29 (d, 2H), 6.94 (d, 2H), 4.56 (s, 2H), 4.15 (m, 1H), 3.87 (s, 3H), 3.74 (dd, 1H), 3.66 (dd, 1H), 2.88 (d, 1H).

Workup

  1. temperatureThe closed vial was heated at 100° C. for 18 h
  2. extractionextracted twice with Et2O
  3. washThe organic phase was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-9839d77ad6414c189dca7fe7b151aff4
Source dataset
uspto-grants-2012_01
Patent number
US08093406B2

Reaction notes

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