Hydrochloric Acid → N-(3-fluorophenyl)-3-[(3-hydroxyphenyl)-piperidin-4-ylidene-methyl]-N-methyl-benzamide

HRID 445034Notes

Reaction equation

HRID 445034 reaction equation
O1CCCC1.Cl.C(OC([N:14]1[CH2:19][CH2:18][C:17](=[C:20]([C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([O:44][Si](C(C)(C)C)(C)C)[CH:39]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27](=[O:37])[N:28]([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=3)[CH3:29])[CH:22]=2)[CH2:16][CH2:15]1)=O)(C)(C)C>O>[F:36][C:32]1[CH:31]=[C:30]([N:28]([CH3:29])[C:27](=[O:37])[C:23]2[CH:24]=[CH:25][CH:26]=[C:21]([C:20]([C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([OH:44])[CH:39]=3)=[C:17]3[CH2:18][CH2:19][NH:14][CH2:15][CH2:16]3)[CH:22]=2)[CH:35]=[CH:34][CH:33]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 699143744-([3-(tert-butyldimethylsilanyloxy)phenyl]{3-[N-(3-fluorophenyl)-N-methylcarbamoyl]phenyl}-methylene)piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 10001962N-(3-fluorophenyl)-3-[(3-hydroxyphenyl)-piperidin-4-ylidene-methyl]-N-methyl-benzamideYield 31.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

Tetrahydrofuran (70 mL) and 3 N HCl (50 mL) were added to the above crude 4-([3-(tert-butyldimethylsilanyloxy)phenyl]{3-[N-(3-fluorophenyl)-N-methylcarbamoyl]phenyl}-methylene)piperidine-1-carboxylic acid tert-butyl ester (2.75 g). The resulting mixture was stirred at 60° C. for 4 h. The reaction mixture was cooled to room temperature, followed by the addition of water (100 mL). The resulting solution was extracted with diethyl ether (100 mL×2). The remaining water layer was neutralized to pH≅9. by 10% NaOH. The water layer became cloudy at this stage. The cloudy water mixture was extracted by n-butanol (100 mL×3). The combined n-butanol layers were washed by water (75 mL×2) and brine (75 mL×1), dried by Na2SO4 and concentrated to give crude product (2.27 g; crude), which was purified to give N-(3-fluorophenyl)-3-[(3-hydroxyphenyl)-piperidin-4-ylidene-methyl]-N-methyl-benzamide (579 mg). 1H NMR (600 MHz, DMSO-d6) δ 9.25 (s, 1H), 7.23 (m, 3H), 7.09 (d, 1H, J=10.0 Hz), 7.03 (dd, 1H, J=8.0, 8.0 Hz), 6.96 (ddd, 1H, J=8.5, 8.5, 2.5 Hz), 6.92 (m, 2H), 6.85 (s, 1H), 6.56 (dd, 1H, J=8.0, 2.0 Hz), 6.34 (s, 1H), 6.31 (d, 1H, J=7.5 Hz), 3.35 (s, 3H), 2.65 (m, 2H), 2.55 (m, 2H), 2.13 (bs, 1H), 2.07 (m, 2H), 1.72 (m, 2H); Found: C, 72.87; H, 6.51; N, 5.86. Calc. C, 72.77; H, 6.62; N, 5.98.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe resulting solution was extracted with diethyl ether (100 mL×2)
  3. extractionThe cloudy water mixture was extracted by n-butanol (100 mL×3)
  4. washThe combined n-butanol layers were washed by water (75 mL×2) and brine (75 mL×1)
  5. dry with materialdried by Na2SO4
  6. concentrationconcentrated
  7. customto give crude product (2.27 g; crude), which
  8. customwas purified

Sources & evidence

ORD record
ord-3804f503a3464a4786e7de1e4e67f419
Source dataset
uspto-grants-2013_07
Patent number
US08476280B2

Reaction notes

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