Hydrochloric Acid → HCID 69695104, compound

HRID 489896Notes

Reaction equation

HRID 489896 reaction equation
C([O:3][C:4]([C@@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([CH:12]2[CH2:17][CH2:16][N:15]([C:18]([C:20]3[CH:25]=[C:24]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[N:23]=[C:22]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH:21]=3)=[O:19])[CH2:14][CH2:13]2)[CH2:7]1)=O)C.O.[OH-].[Li+].Cl.[N:42]1([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]1.C(N(CC)C(C)C)(C)C>O1CCCC1.O.ClCCl.C1(C)C(C)=CC=CC=1.ClCCl.CO>[C:51]([O:50][C:48]([N:42]1[CH2:47][CH2:46][N:45]([C:4]([CH:6]2[CH2:11][CH2:10][CH2:9][N:8]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([C:20]4[CH:25]=[C:24]([C:26]5[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=5)[N:23]=[C:22]([C:32]5[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=5)[CH:21]=4)=[O:19])[CH2:14][CH2:13]3)[CH2:7]2)=[O:3])[CH2:44][CH2:43]1)=[O:49])([CH3:54])([CH3:53])[CH3:52]

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 168937Lithium hydroxide, monohydrateHCID 69695071HCID 69695071, compound

Product 1

HCID 69695104HCID 69695104, compoundYield 71%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 7237O-XyleneSolventHCID 8028TetrahydrofuranSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

(3R)-1′-[2,6-Diphenyl-pyridine-4-carbonyl]-[1,4′]bipiperidinyl-3-carboxylic acid ethyl ester (1.96 g, 3.94 mmol) was dissolved in tetrahydrofuran (20 mL) and lithium hydroxide monohydrate (3 eq, 0.5 g) in water (10 mL) was added. The two phase mixture was stirred for 16 hr at ambient temperature. Thin layer chromatography (19:1 dichloromethane-methanol) indicated no remaining starting material. 2M hydrochloric acid (6 mL) was added to adjust the pH to ˜5, about 2× the volume of the xylene was added and the mixture was evaporated to give a pale oil. This was further dried briefly under high vacuum then suspended in ethanol-free chloroform (˜30 mL), thionyl chloride added (5 mL) and the mixture heated under reflux, directing the evolved gases to a scrubber. After 30 minutes a further aliquot of thionyl chloride (5 mL) and chloroform (20 mL) were added and the reflux continued. After all the solid had dissolved (˜2 hr) the solvent was evaporated under vacuum. Anhydrous dichloromethane (30 mL) was added followed by a mixture of tert-butyl 1-piperazinecarboxylate (1.1 eq, 810 mg) and N,N-diisopropylethylamine (5 eq, 3.4 mL) in anhydrous dichloromethane (10 mL) was added. The cloudy mixture was stirred for 16 hr at ambient temperature then washed with 0.1M sodium hydroxide solution and the aqueous layer was extracted with dichloromethane (×3). The combined organic layers were dried over anhydrous sodium sulfate and evaporated to dryness under vacuum. The residue was purified by chromatography on 100 g silica gel/5% methanol-dichloromethane to give the title compound (1.78 g, 71%).

Workup

  1. customthe mixture was evaporated
  2. customto give a pale oil
  3. customThis was further dried briefly under high vacuum
  4. additionthionyl chloride added (5 mL)
  5. temperaturethe mixture heated
  6. temperatureunder reflux
  7. additionAfter 30 minutes a further aliquot of thionyl chloride (5 mL) and chloroform (20 mL) were added
  8. dissolutionAfter all the solid had dissolved (˜2 hr) the solvent
  9. customwas evaporated under vacuum
  10. additionAnhydrous dichloromethane (30 mL) was added
  11. additionwas added
  12. stirringThe cloudy mixture was stirred for 16 hr at ambient temperature
  13. washthen washed with 0.1M sodium hydroxide solution
  14. extractionthe aqueous layer was extracted with dichloromethane (×3)
  15. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  16. customevaporated to dryness under vacuum
  17. customThe residue was purified by chromatography on 100 g silica gel/5% methanol-dichloromethane

Sources & evidence

ORD record
ord-2afe3850783243e697484b9fc8c44493
Source dataset
uspto-grants-2005_12
Patent number
US06979741B2

Reaction notes

Loading…