Acetic Acid → 1-Cyclohexyl-4-(4-(2-methoxyphenyl)piperazin-1-yl)-2-methyl-2-phenylbutan-1-one

HRID 890993Notes

Reaction equation

HRID 890993 reaction equation
[C:1]1([C:7]([C:12]([CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)=[O:13])([CH3:11])[CH2:8][CH:9]=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[CH3:21][O:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH3:21][O:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[N:29]1[CH2:34][CH2:33][N:32]([CH2:9][CH2:8][C:7]([C:12]([CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)=[O:13])([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH3:11])[CH2:31][CH2:30]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 9899402N-(2-Methoxyphenyl)piperazine hydrochlorideHCID 117801924-Cyclohexyl-3-methyl-4-oxo-3-phenylbutanal

Product 1

HCID 98029871-Cyclohexyl-4-(4-(2-methoxyphenyl)piperazin-1-yl)-2-methyl-2-phenylbutan-1-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-Phenyl-3-cyclohexanecarbonyl-butan-1-al (57.8 g, 224 mmol) was dissolved in methylene chloride (1650 mL) followed by addition of 1-(2-methoxyphenyl)piperazine hydrochloride (56.3 g, 246 mmol). Acetic acid (41 mL) may optionally be added to turn the slurry into a solution. To the stirred solution, sodium triacetoxyborohydride (60.3 g, 284 mmol) was slowly added. A slight exotherm resulted and a slurry was produced. The reaction mixture was stirred for an additional 3 hours at room temperature. The reaction was then quenched by addition of 2.0 N sodium hydroxide (1050 mL) producing a pH of about 10 for the quenched reaction mixture. The mixture was then extracted with methylene chloride (2 times, 1L and 300 mL). The organic extracts were combined, washed successively with 1.0 N HCl (600 mL), 1.0 N sodium hydroxide (600 mL), brine (600 mL), dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum to provide the final title compound as a thick oil; UV (MeOH): λmax=243 nm, ε243=7110; λmax=281 nm, ε281=3200; IR (CDCl3, cm−1) 2937, 2856, 2836, 1698, 1499, 1451, 1377, 1316, 1242, 1029; 1H NMR (300 MHz, DMSO) δ 7.75 (2H, m), 7.55 (2H, m), 6.93 (3H, m), 6.85 (2H, m), 3.75 (3H, s), 2.90 (4H, m), 2.43 (4H, m), 2.08 (5H, m), 1.5 (10H, m), 1.05 (3H, m); 13C NMR (300 MHz, DMSO) δ 214.18, 151.94, 141.25, 141.23, 128.45, 126.85, 126.74, 122.22, 120.79, 117.81, 111.97, 55.28, 54.54, 53.67, 53.13, 50.01, 45.30, 33.75, 30.44, 30.12, 25.21, 24.98, 24.93, 19.94. Anal. Calcd for C28H38N2O2: C, 77.38; H, 8.81; N, 6.45. Found: C, 76.44; H, 8.89; N, 6.01.

Workup

  1. customA slight exotherm resulted
  2. customa slurry was produced
  3. customThe reaction was then quenched by addition of 2.0 N sodium hydroxide (1050 mL)
  4. customproducing a pH of about 10
  5. customfor the quenched reaction mixture
  6. extractionThe mixture was then extracted with methylene chloride (2 times, 1L and 300 mL)
  7. washwashed successively with 1.0 N HCl (600 mL), 1.0 N sodium hydroxide (600 mL), brine (600 mL)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-cb8636621c3a4e0e87a8cd4569fe3c53
Source dataset
uspto-grants-2006_02
Patent number
US07001908B2

Reaction notes

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