Hydrochloric Acid → HCID 25024042, compound

HRID 1645317Notes

Reaction equation

HRID 1645317 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:13](=O)[C:12]3[CH:15]=[C:16]([O:19][C:20](=[O:26])[N:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[CH:17]=[CH:18][C:11]=3[C:10]=2[O:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH2:36][N:37]3[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]3)=[CH:30][CH:29]=2)=[CH:5][CH:4]=1.Cl.C([O-])(O)=O.[Na+].C(Cl)Cl>C(O)CC.CCCCCC.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[S:13][C:12]3[CH:15]=[C:16]([O:19][C:20](=[O:26])[N:21]([CH2:22][CH3:23])[CH2:24][CH3:25])[CH:17]=[CH:18][C:11]=3[C:10]=2[O:27][C:28]2[CH:29]=[CH:30][C:31]([O:34][CH2:35][CH2:36][N:37]3[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]3)=[CH:32][CH:33]=2)=[CH:7][CH:8]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 44249710HCID 44249710, compound

Product 1

HCID 25024042HCID 25024042, compound

Reagents, catalysts & solvents 3

HCID 10311-PropanolSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Dissolve diethyl-carbamic acid 2-(4-methoxy-phenyl)-1-oxo-3-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-1H-1Lambda*4*-benzo[b]thiophen-6-yl ester (Example 1) (4.0 g, 6.8 mmol) in 80 mL n-propyl alcohol with stirring and then cool the resultant solution to −10° C. Add 37% hydrochloric acid (6.7 g, 67 9 mmol) dropwise at −10° C. within a 10 minute time period. After the mixture is warmed up to ambient temperature, add Na2S2O3.5H2O (6.7 g, 27 0 mmol) and allow the reaction to occur at ambient temperature for 4 hours. Monitor the reaction by 11H NMR for completion. Carefully add 100 mL of saturated aqueous NaHCO3 to neutralize the reaction mixture and then adjust the pH of the mixture to 7. Add 100 mL CH2Cl2 and stir. Separate the organic phase, and extract the aqueous phase with CH2Cl2 (2×50 mL). Wash (with successive washes) the combined organic phase with brine (50 mL) and water (50 mL), dry over anhydrous Na2SO4, and filter. Remove all the volatiles under reduced pressure, affording 3.4 g of the crude product as a viscous material. Pass this viscous material through a short pad of silica gel with 100% petroleum ether (30-60° C.) and 100% ethyl acetate as the eluents. Collect the ethyl acetate phase and evaporate all the volatiles under reduced pressure, producing 3.2 g of the crude product as a pale yellow viscous material. Add 20 mL of hexane and the mixture is kept at 4° C. overnight, affording the desired product Diethyl-carbamic acid 2-(4-methoxy-phenyl)-3-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-benzo[b]thiophen-6-yl ester as a white solid (2.9 g, yield 74%, NMR purity>96%) after dried at 40° C./2 mmHg.

Workup

  1. customthe reaction
  2. customMonitor the reaction by 11H NMR for completion
  3. stirringstir
  4. customSeparate the organic phase
  5. extractionextract the aqueous phase with CH2Cl2 (2×50 mL)
  6. washWash (with successive washes) the combined organic phase with brine (50 mL) and water (50 mL)
  7. dry with materialdry over anhydrous Na2SO4
  8. filtrationfilter
  9. customRemove all the volatiles under reduced pressure
  10. customaffording 3.4 g of the crude product as a viscous material
  11. customCollect the ethyl acetate phase
  12. customevaporate all the volatiles under reduced pressure
  13. customproducing 3.2 g of the crude product as a pale yellow viscous material
  14. waitthe mixture is kept at 4° C. overnight

Sources & evidence

ORD record
ord-221eda037cf64404a12e6616ae63a1c4
Source dataset
uspto-grants-2012_02
Patent number
US08124776B2

Reaction notes

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