3,4-dihydro-2H-pyran → 2-(3-fluorophenoxy)tetrahydro-2H-pyran

HRID 855156Notes

Reaction equation

HRID 855156 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.[O:9]1[CH:14]=[CH:13][CH2:12][CH2:11][CH2:10]1>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[O:8][CH:10]1[CH2:11][CH2:12][CH2:13][CH2:14][O:9]1

Participants

3

Reactant 2

HCID 80803,4-dihydro-2H-pyranHCID 97433-Fluorophenol

Product 1

HCID 157823112-(3-fluorophenoxy)tetrahydro-2H-pyranYield 78%

Procedure

To 75 g (669 mmol) of 3-fluorophenol at -35 ° C. was added 79 g (928 mmol) of 3,4-dihydro-2H-pyran. The ice bath was removed and added 1.0 mL of concentrated HCl. The temperature was allowed to warm to room temperature and the reaction progress was monitored by HPLC. 500 ml of diethyl ether and 500 mL of 1 M NaHCO3 were added to the reaction. The organic layers were washed with NaHCO3 (2×) and brine. The organic layers were dried over Na2SO4, filtered, and concd to afford a yellow oil which was purified by silica gel chromatography with EtOAc/hexane (1:9). Concentration of the desired fractions afforded 102.1 g (78%) of a white solid: 1H NMR (CDCl3/400 MHz) 1.56-2.03 (m, 6H), 3.58-3.63 (m, 1H), 3.85-3.91 (m, 1H), 5.39 (t, 1H, J=3.2 Hz), 6.65-6.70 (m, 1H), 6.78-6.84 (m, 2H), 7.21 (dd, 1H, J=8.2, 15.0 Hz); HRMS (EI+) m/z calcd for (C11H13FO2) 196.0900, found 196.0890.

Workup

  1. customThe ice bath was removed
  2. additionadded 1.0 mL of concentrated HCl
  3. addition500 ml of diethyl ether and 500 mL of 1 M NaHCO3 were added to the reaction
  4. washThe organic layers were washed with NaHCO3 (2×) and brine
  5. dry with materialThe organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. customconcd to afford a yellow oil which
  8. customwas purified by silica gel chromatography with EtOAc/hexane (1:9)

Sources & evidence

ORD record
ord-05c013e368e6450eb407c3ac84dcbaf3
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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