HCID 57040521, compound → HCID 57161946, compound

HRID 1460084Notes

Reaction equation

HRID 1460084 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 97.3%

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 (Example 2) (35.00 g, 0.0843 mol) in 400 mL anhydrous tetrahydrofuran was cooled to -78° C. n-Butyllithium (1.6M in hexane, 126 mL, 0.20 mol) was added dropwise. The reaction was stirred for 30 min. at -78° C. and then quenched with saturated ammonium chloride. After warming to room temperature, the reaction mixture was poured into 1000 mL ethyl acetate:1000 mL water. The ethyl acetate layer was washed with brine and dried over sodium sulfate. The solvent was removed to give 27.6 g of pink solid. The solid was recrystallized from ethyl acetate giving 19.4 g (68%) of (±)-3-((αR*)-α-((2R*,5S*)-4-allyl-2,5-dimethyl-1-piperazinyl)benzyl)phenol as a white solid, mp 172.5°-175.5° C. NMR (200 MHz, DMSO-d6): δ 0.96 (d, J=6 Hz, 3H); 1.08 (d, J=6 Hz, 3H); 1.85 (t, J=11 Hz, 1H); 2.09 (t, J=11 Hz, 1H); 2.5-2.9 (m, 5H); 3.15 (dd, J=5.4 Hz and 15, 1H); 4.9 (s, 1H); 5.1-5.2 (2d, 2H); 5.7-5.9 (m, 1H); 6.55 (d, J=8 Hz, 1H); 6.8 (d, J=8 Hz, 1H); 6.85 (s, 1H); 7.07 (t, J=8 Hz, 1H); 7.2-7.4 (m, 5H); 9.3 (s, 1H). The free amine was dissolved in ethanol and converted to the monohydrochloride salt by titration to pH of 3.8 with ethanolic hydrogen chloride. The salt was precipitated from ethanol with diethyl ether to give 15.82 g as a white solid. Calc. for C22 H28N2O HCl 0.5 H2O: C, 69.18; H, 7.92; N, 7.33; Cl, 9.28. Found: C, 69.55; H, 8.03; N, 7.31; Cl, 9.27.

Workup

  1. additionwas added dropwise
  2. customquenched with saturated ammonium chloride
  3. temperatureAfter warming to room temperature
  4. additionthe reaction mixture was poured into 1000 mL ethyl acetate
  5. washThe ethyl acetate layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was removed

Sources & evidence

ORD record
ord-0b4da8e7f43f44e4baf78c1a54b29e16
Source dataset
uspto-grants-1998_12
Patent number
US05854249

Reaction notes

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