Water → HCID 66664162, compound

HRID 407147Notes

Reaction equation

HRID 407147 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([O:7][C:8](=[O:22])[NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:3][CH2:2]1.[C:23]([O-:26])(O)=[O:24].[Na+].[OH-].[Na+].O>CC1OCCC1>[CH2:16]([O:26][C:23]([CH2:6][NH:1][CH2:2][CH2:3][N:1]1[CH2:2][CH2:3][CH:4]([O:7][C:8](=[O:22])[NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:5][CH2:6]1)=[O:24])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:10]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 516892Sodium Bicarbonate2×HCID 10851461Biphenyl-2-ylcarbamic Acid Piperidin-4-yl Ester

Product 1

HCID 66664162HCID 66664162, compound

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent2×

Conditions

Temperature
30 °C

Procedure

The product from the previous step (in MeTHF) and biphenyl-2-yl-carbamic acid piperidin-4-yl ester (10.0 kg, 32.6 mol, 1.0 eq.) in MeTHF (28.5 kg) were placed in the reaction vessel and heated to 30° C. for one hour. The mixture was then cooled to 5° C. NaHB(OAc)3 (10.0 kg, 45.8 mol, 1.4 eq.) was added portion wise over a period of 40 minutes while maintaining the temperature below 20° C. The mixture was then stirred for 30 minutes. Additional NaHB(OAc)3 (0.5 kg) was added the reaction allowed to progress to completion. A saturated solution of NaHCO3 (14.3 kg, 15.3 mol, 1.1 volumes) was added and stirred for 10 minutes. The aqueous phase was separated and discarded. A 33% NaOH solution (15.8 kg, 129.9 mol, 4.0 eq.) was added to the reaction mixture to adjust the pH to be in the range of 8-12. Water (40 kg) was added in two portions, after which phase separation occurred. A saturated NaHCO3 (7.1 kg, 7.6 mol, 0.7 volumes) was added to the reaction mixture and stirred for 10 minutes. The aqueous phase was separated and discarded. Additional water (4.9 kg) was added to dissolve any remaining salts and a vacuum distillation was conducted at a maximum temperature of 45° C. to remove part of the solvent (7.2 volumes). MeOH (56.1 kg, 7.2 volumes) was added to the reaction mixture before continuing with the next step.

Workup

  1. temperatureThe mixture was then cooled to 5° C
  2. temperaturewhile maintaining the temperature below 20° C
  3. stirringstirred for 10 minutes
  4. customThe aqueous phase was separated
  5. customafter which phase separation
  6. stirringstirred for 10 minutes
  7. customThe aqueous phase was separated
  8. additionAdditional water (4.9 kg) was added
  9. dissolutionto dissolve any remaining salts
  10. distillationa vacuum distillation
  11. customwas conducted at a maximum temperature of 45° C.
  12. customto remove part of the solvent (7.2 volumes)
  13. additionMeOH (56.1 kg, 7.2 volumes) was added to the reaction mixture

Sources & evidence

ORD record
ord-b85ef76c8afc4f5db24ae91996583e91
Source dataset
uspto-grants-2014_06
Patent number
US08754225B2

Reaction notes

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