Phenol → 1-Cycloheptyl-3,3-dimethyl-4-(phenoxymethyl)pyrrolidin-2-one

HRID 2115605Notes

Reaction equation

HRID 2115605 reaction equation
[CH:1]1([N:8]2[CH2:12][CH:11]([CH2:13][OH:14])[C:10]([CH3:16])([CH3:15])[C:9]2=[O:17])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:18]1(O)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C1(C)C=CC=CC=1>[CH:1]1([N:8]2[CH2:12][CH:11]([CH2:13][O:14][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:10]([CH3:15])([CH3:16])[C:9]2=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1

Participants

6

Reactant 4

HCID 996PhenolHCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 666652881-Cycloheptyl-4-hydroxymethyl-3,3-dimethyl-pyrrolidin-2-one

Product 1

HCID 248899031-Cycloheptyl-3,3-dimethyl-4-(phenoxymethyl)pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

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)+.

Workup

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

Sources & evidence

ORD record
ord-fd35b58a6b3849d89cc9c502e4948cbe
Source dataset
uspto-grants-2008_10
Patent number
US07435833B2

Reaction notes

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