Water → HCID 25208190, compound

HRID 1452710Notes

Reaction equation

HRID 1452710 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([NH:11][CH:12]1[CH2:17][CH2:16][N:15]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:14][CH2:13]1)=[O:10].CN1CCOCC1.Cl[C:33]([O:35][CH3:36])=[O:34].O>CC1CCCO1>[CH3:36][O:35][C:33]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([NH:11][CH:12]1[CH2:17][CH2:16][N:15]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:14][CH2:13]1)=[O:10])=[O:34]

Participants

6

Reactant 4

HCID 962WaterHCID 6586Methyl chloroformateHCID 79724-MethylmorpholineHCID 24815128HCID 24815128, compound

Product 1

HCID 25208190HCID 25208190, compound

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Conditions

Temperature
-12 °C

Procedure

50 ml of 2-methyltetrahydrofuran are distilled off from the solution consisting of 9.15 g (28.29 mmol, 1.0 eq) 2-amino-N-[1-(phenylmethyl)-4-piperidinyl]-phenylacetamide in 162 ml of 2-methyltetrahydrofuran. The solution is cooled to −12° C. and 4.56 g (45.10 mmol, 1.6 eq) 4-methylmorpholine are added, followed by 4.26 g (45.10 mmol, 1.6 eq) methyl chloroformate. The reaction mixture is stirred for another 1 hour at 20° C. and then combined with 100 ml of water. After phase separation the aqueous phase is washed with 20 ml 2-methyltetrahydrofuran and the combined organic phases are washed with 50 ml of water. The organic solvent is distilled off in vacuo. The residue is combined with 50 ml of acetone and refluxed. Then 100 ml of water are added and the suspension obtained is cooled to 20° C. To complete the crystallisation the mixture is stirred for 30 minutes at 20° C. Then the product is suction filtered, washed with 30 ml acetone-water mixture (1:2) and dried in the dryer at 45° C. while being rendered inert.

Workup

  1. distillation50 ml of 2-methyltetrahydrofuran are distilled off from the solution
  2. customAfter phase separation the aqueous phase
  3. washis washed with 20 ml 2-methyltetrahydrofuran
  4. washthe combined organic phases are washed with 50 ml of water
  5. distillationThe organic solvent is distilled off in vacuo
  6. temperaturerefluxed
  7. additionThen 100 ml of water are added
  8. customthe suspension obtained
  9. temperatureis cooled to 20° C
  10. customthe crystallisation the mixture
  11. stirringis stirred for 30 minutes at 20° C
  12. filtrationfiltered
  13. washwashed with 30 ml acetone-water mixture (1:2)
  14. customdried in the dryer at 45° C.

Sources & evidence

ORD record
ord-82a631e46acf4b84a5cc3c5d45a0e555
Source dataset
uspto-grants-2009_01
Patent number
US07473778B2

Reaction notes

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