Reaction #44485

Reaction equation

di-tert-butyl azodicarboxylate

solution

1-Cycloheptyl-4-hydroxymethyl-3,3-dimethyl-pyrrolidin-2-one

phenol

triphenyl phosphine

→

title compound

1-cycloheptyl-3,3-dimethyl-4-(phenoxymethyl)pyrrolidin-2-one

Solvents

Toluene

Conditions

Workup

1. 1
   workup.ADDITIONwas added
2. 2
   OtherThe reaction mixture was partitioned between toluene and water
3. 3
   OtherThe organic phase was separated
4. 4
   Othersolvent evaporated in vacuo
5. 5
   OtherThe crude reaction mixture
6. 6
   Otherwas purified by preparative reverse phase HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 um particle size)

Procedure

A solution of Example 3A (50 mg, 0.2 mmoles), phenol (23.5 mg, 0.25 mmoles), and triphenyl phosphine (85.8 mg, 0.33 mmoles) was stirred in anhydrous Toluene (1.25 mL). To the reaction, di-tert-butyl azodicarboxylate (76.9 mg, 0.33 mmoles) was added and heated to 80° C. for one hour. The reaction mixture was partitioned between toluene and water. The organic phase was separated and solvent evaporated in vacuo. The crude reaction mixture was purified by preparative reverse phase HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 um particle size) using a gradient of 20% to 100% acetonitrile:water (0.1% trifluoroacetic acid) over eighteen minutes at a flow rate of 40 mL/minute to provide the title compound. 1H NMR (500 MHz, CDCl3) δ ppm 7.27-7.32 (m, 2H), 6.95-6.99 (m, 1H), 6.88-6.91 (m, 2H), 4.06-4.19 (m, 1H), 4.07 (dd, J=9.15, 5.65 Hz, 1H), 3.92 (t, J=8.77 Hz, 1H), 3.51 (dd, J=9.92, 7.63 Hz, 1H), 3.13 (dd, J=9.76, 7.78 Hz, 1H), 2.45 (qd, J=7.86, 5.72 Hz, 1H), 1.43-1.82 (m, 12H), 1.25 (s, 3H), 1.05 (s, 3H). MS (APCI+) m/z 316.2 (M+H)+.

Source