HCID 57040521, compound → HCID 57161946, compound

HRID 2258354Notes

Reaction equation

HRID 2258354 reaction equation
[CH2:1]([N:4]1[C@@H:9]([CH3:10])[CH2:8][N:7]([C@@H:11]([C:19]2[CH:20]=[C:21]([OH:25])[CH:22]=[CH:23][CH:24]=2)[C:12]2[CH:17]=[CH:16][C:15](Br)=[CH:14][CH:13]=2)[C@H:6]([CH3:26])[CH2:5]1)[CH:2]=[CH2:3].C([Li])CCC>O1CCCC1>[CH2:1]([N:4]1[C@@H:9]([CH3:10])[CH2:8][N:7]([C@@H:11]([C:19]2[CH:20]=[C:21]([OH:25])[CH:22]=[CH:23][CH:24]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C@H:6]([CH3:26])[CH2:5]1)[CH:2]=[CH2:3]

Participants

4

Reactant 2

HCID 57040521HCID 57040521, compoundHCID 178418339Butyllithium

Product 1

HCID 57161946HCID 57161946, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of (-)-3-((αR)-α-((2R,5S)-4-allyl-2,5-dimethyl-1-piperazinyl)-4-bromobenzyl)phenol (3.00 g, 7.2 mmol), from Example 70, in 80 mL of dry tetrahydrofuran was cooled to -78° C. n-Butyllithium (9.9 mL of a 1.6M solution in hexanes) was added at a rate to keep the temperature below -70° C. After stirring at -78° C. for 30 minutes, the reaction was quenched with 15 mL of saturated aqueous ammonium chloride, warmed to room temperature, diluted with water and extracted with ethyl acetate. The ethyl acetate extracts were combined, dried over sodium sulfate, and the solvent removed under vacuum to give a white solid which was recrystallized from acetonitrile to give 2.11 g (88%) of (-)-3-((αR)-α-((2R,5S)-4-allyl-2,5-dimethyl-1-piperazinyl)benzyl)phenol as white crystals, mp 195°-197° C., [α]D20 =-2.8° (tetrahydrofuran, c=1.6). HPLC on β-cyclodextrin with methanol:0.1M ammonium acetate/1:1 gave one peak at tR =8.4 min. NMR (DMSO-d6, 200 MHz): δ0.95 (d, J=6 Hz, 3H); 1.1 (d, J=6 Hz, 3H); 1.8 (dd, J1 =7 Hz, J2 =11 Hz, 1H); 2.1 (dd, J1 =7 Hz, J2 =9 Hz, 1H); 2.4-2.8 (m, 4H); 2.9 (dd, J1 7 Hz, J2 =14 Hz, 1H); 3.15 (dd, J1 =5 Hz, J2 =14 Hz, 1H); 4.95 (s, 1H); 5.1 (d, J=10 Hz, 1H); 5.2 (d, J=18 Hz, 1H); 5.8 (m, 1H); 6.6 (d, J=8 Hz, 1H); 6.8 (d, J=8 Hz, 1H); 6.95 (s, 1H); 7.1 (t, J=8 Hz, 1H); 7.3 (m, 5H); 9.3 (s, 1H). Mass spectrum (Cl--CH4) m/z: 337 (M+1, 69%); 336 (M+, 15%); 183 (100%); 153 (92%). Calc. for C22H28N2O: C, 78.53; H, 8.39; N, 8.33. Found: C, 78.37; H, 8.47; N, 8.38.

Workup

  1. additionwas added at a rate
  2. customthe temperature below -70° C
  3. customthe reaction was quenched with 15 mL of saturated aqueous ammonium chloride
  4. temperaturewarmed to room temperature
  5. additiondiluted with water
  6. extractionextracted with ethyl acetate
  7. dry with materialdried over sodium sulfate
  8. customthe solvent removed under vacuum
  9. customto give a white solid which
  10. customwas recrystallized from acetonitrile

Sources & evidence

ORD record
ord-5ef199bb3fba477781761433ccaa1d92
Source dataset
uspto-grants-1997_08
Patent number
US05658908

Reaction notes

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