3-Fluorophenol → 1-Benzhydryl-3-(3-fluorophenoxy)azetidine

HRID 1066902Notes

Reaction equation

HRID 1066902 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].[C:15]1([CH:21]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:22]2[CH2:25][CH:24](S(C)(=O)=O)[CH2:23]2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C(#N)C>[CH:21]([N:22]1[CH2:25][CH:24]([O:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)[CH2:23]1)([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 97433-FluorophenolHCID 11430Potassium CarbonateHCID 155219691-Benzhydryl-3-(methylsulfonyl)azetidine

Product 1

HCID 197996211-Benzhydryl-3-(3-fluorophenoxy)azetidineYield 29.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 3.9 g (0.035 mol) of 3-fluorophenol in 250 mL of acetonitrile, was added 6.3 g (0.045 mol) of K2CO3 followed by 12.25 g (0.039 mol) of 1-(diphenylmethyl)-3-methane sulfonyl azetidine, prepared according to the procedure of Example 1a, Step 4. The reaction mixture was heated at 75° C. for 18 h. The solvent was removed under vacuo, and the residue was taken up in a mixture of ether and water. The aqueous layer was extracted with ether, the combined extracts were dried over magnesium sulfate, and the solvent was removed under vacuo. The product was filtered through 500 mL of silica gel, eluted with 50% CH2Cl2/hexane then 15% ethyl acetate/hexane to give 3.4 g of the title compound: mp 81-82° C. 1H NMR (300 MHz, CDCl3) δ 3.17 (dd, 2H), 3.72 (dd, 2H), 4.46 (s, 1H), 4.77 (m, 1H), 6.48 (dd, 1H), 6.53 (dd, 1H), 6.63 (m, 1H), 7.22 (m, 3H), 7.29 (m, 4H), 7.31 (dd, 4H); MS (ES) m/z (relative intensity): 334 (M++H).

Workup

  1. customprepared
  2. customThe solvent was removed under vacuo
  3. additionthe residue was taken up in a mixture of ether and water
  4. extractionThe aqueous layer was extracted with ether
  5. dry with materialthe combined extracts were dried over magnesium sulfate
  6. customthe solvent was removed under vacuo
  7. filtrationThe product was filtered through 500 mL of silica gel
  8. washeluted with 50% CH2Cl2/hexane

Sources & evidence

ORD record
ord-66ca0a01ddf14e31a8984b97124d4db1
Source dataset
uspto-grants-2001_06
Patent number
US06245799B1

Reaction notes

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