Acetic Acid → Biphenyl-2-yl-carbamic acid 1-{2-[(4-carbamoylbenzoyl)methylamino]ethyl}piperidin-4-yl ester

HRID 407149Notes

Reaction equation

HRID 407149 reaction equation
[NH:1]1CCC(C(N)=O)CC1.[CH:10]([C:12]1[CH:45]=[CH:44][C:15]([C:16]([CH2:18][NH:19][CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][CH:25]([O:28][C:29](=[O:43])[NH:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH2:24][CH2:23]2)=[O:17])=[CH:14][CH:13]=1)=[O:11].[O-]S([O-])(=O)=O.[Na+].[Na+].CC(O)=O>CC(O)C>[C:10]([C:12]1[CH:13]=[CH:14][C:15]([C:16]([CH2:18][NH:19][CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][CH:25]([O:28][C:29](=[O:43])[NH:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH2:24][CH2:23]2)=[O:17])=[CH:44][CH:45]=1)(=[O:11])[NH2:1]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 37724-PiperidinecarboxamideHCID 24436Sodium SulfateHCID 57436143Biphenyl-2-ylcarbamic Acid 1-{2-[(4-Formylbenzoyl)methylamino]ethyl}piperidin-4-yl Ester

Product 1

HCID 66663886Biphenyl-2-yl-carbamic acid 1-{2-[(4-carbamoylbenzoyl)methylamino]ethyl}piperidin-4-yl ester

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
30 °C

Procedure

Isonipecotamide (15.4, 120 mmol, 2.0 eq.) and IPA (200 mL) were added to the solution of biphenyl-2-yl-carbamic acid 1-{2-[(4-formylbenzoyl)methylamino]ethyl}piperidin-4-yl ester from the previous step. Liquid (200 mL) was distilled off and additional IPA (400 mL) was added under reduced pressure at 60° C. Liquid (400 mL) was distilled off over a period of 1.5 hours and additional IPA (600 mL) was added. Liquid (100 mL) was distilled off and the remaining solution was cooled to 30° C. to yield a hazy white mixture, which was then added to Na2SO4 (18 g). The flask was rinsed with IPA (100 mL) and added to the solution. The resulting mixture was cooled to room temperature and AcOH (20 mL, 360 mmol, 6.0 eq.) was added. The mixture was cooled to 18° C. with an ice bath and NaHB(OAc)3 (38.2 g, 180 mmol, 3.0 eq.) was added over 5 minutes. The mixture was allowed to warm up to 25° C. and was maintained at that temperature for 2 hours. Solvent was removed under reduced pressure, and the remaining material was used directly in the next step.

Workup

  1. distillationLiquid (200 mL) was distilled off
  2. additionadditional IPA (400 mL) was added under reduced pressure at 60° C
  3. distillationLiquid (400 mL) was distilled off over a period of 1.5 hours
  4. additionadditional IPA (600 mL) was added
  5. distillationLiquid (100 mL) was distilled off
  6. customto yield a hazy white mixture, which
  7. washThe flask was rinsed with IPA (100 mL)
  8. additionadded to the solution
  9. temperatureThe resulting mixture was cooled to room temperature
  10. temperatureThe mixture was cooled to 18° C. with an ice bath
  11. temperatureto warm up to 25° C.
  12. temperaturewas maintained at that temperature for 2 hours
  13. customSolvent was removed under reduced pressure

Sources & evidence

ORD record
ord-884f98adf33c4248a6b5c68cb4274042
Source dataset
uspto-grants-2014_06
Patent number
US08754225B2

Reaction notes

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