Acetic Acid → tert-Butyl trans(+/-)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-(ethylamino)piperidine-1-carboxylate

HRID 43858Notes

Reaction equation

HRID 43858 reaction equation
[CH2:1]([NH2:3])[CH3:2].O1CCCC1.[Cl:9][C:10]1[N:11]=[C:12]([C:17]([NH:19][CH:20]2[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][C:21]2=O)=[O:18])[NH:13][C:14]=1[CH2:15][CH3:16].C([BH3-])#N.[Na+].C(O)(=O)C>>[Cl:9][C:10]1[N:11]=[C:12]([C:17]([NH:19][C@@H:20]2[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][C@H:21]2[NH:3][CH2:1][CH3:2])=[O:18])[NH:13][C:14]=1[CH2:15][CH3:16]

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 66726184Ethylamine tetrahydrofuran2×HCID 68406285tert-Butyl 4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-oxopiperidine-1-carboxylate

Product 1

HCID 86648794tert-Butyl trans(+/-)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-(ethylamino)piperidine-1-carboxylateYield 46%

Conditions

Temperature
70 °C

Procedure

A 2 N ethylamine/tetrahydrofuran solution (5 mL) was added to tert-butyl 4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-oxopiperidine-1-carboxylate obtained in Example (201c) (102 mg, 0.275 mmol), and the mixture was heated under reflux at 70° C. for four hours. The reaction solution was concentrated under reduced pressure, and then tetrahydrofuran (2 mL) and methanol (2 mL) were added. A 2 N ethylamine-tetrahydrofuran solution (138 μL), sodium cyanoborohydride (86.4 mg, 1.38 mmol) and acetic acid (110 μL, 1.93 mmol) were added, and the mixture was stirred at room temperature for 15 hours. The reaction solution was concentrated under reduced pressure, and aqueous saturated sodium bicarbonate solution was added to the residue, followed by extraction with chloroform. The resulting organic layer was dried over anhydrous sodium sulfate, and then the insoluble matter was separated by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (eluent: chloroform:methanol=10:1 v/v) to obtain 46 mg of the cis isomer of the title compound (42%) as a pale yellow oily substance and 51 mg of the trans isomer of the title compound (46%) as a pale yellow oily substance.

Workup

  1. temperaturethe mixture was heated
  2. concentrationThe reaction solution was concentrated under reduced pressure
  3. additiontetrahydrofuran (2 mL) and methanol (2 mL) were added
  4. concentrationThe reaction solution was concentrated under reduced pressure, and aqueous saturated sodium bicarbonate solution
  5. additionwas added to the residue
  6. extractionfollowed by extraction with chloroform
  7. dry with materialThe resulting organic layer was dried over anhydrous sodium sulfate
  8. customthe insoluble matter was separated by filtration
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. customthe resulting residue was purified by silica gel column chromatography (eluent: chloroform:methanol=10:1 v/v)

Sources & evidence

ORD record
ord-f550dca08903451db5ff212825958597
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

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