O-Phenylenediamine → (R)-tert-Butyl 3-(2-aminophenylcarbamoyl)piperidine-1-carboxylate

HRID 1096595Notes

Reaction equation

HRID 1096595 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([C:14]([OH:16])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:17]1([NH2:24])[C:18]([NH2:23])=[CH:19][CH:20]=[CH:21][CH:22]=1.CN1CCOCC1.Cl.C(N=C=NCCCN(C)C)C.N1(O)C2C=CC=CC=2N=N1>O.CN(C=O)C>[NH2:23][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[NH:24][C:14]([C@@H:10]1[CH2:11][CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]1)=[O:16]

Participants

8

Reactant 5

HCID 7243O-PhenylenediamineHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 6435161-(1,1-Dimethylethyl) (3R)-1,3-piperidinedicarboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 59918936(R)-tert-Butyl 3-(2-aminophenylcarbamoyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(R)-1-(tert-Butoxycarbonyl)piperidine-3-carboxylic acid (17.45 mmol, 4.0 g) and benzene-1,2-diamine (17.45 mmol, 1.87 g) were added to a 100 mL round-bottomed flask equipped for stirring under nitrogen. DMF (30 mL) and 4-methylmorpholine (52.35 mmol, 5.76 mL) were added and the resultant solution was allowed to stir for 5 min at room temperature. N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (20.94 mmol, 4.01 g) and 1H-benzo[d][1,2,3]triazol-1-ol (20.94 mmol, 2.83 g) were then added and the reaction was allowed to stir at room temperature for 16 hr. The reaction solution was poured into water and extracted with ethyl acetate. The organic layer was washed three times with water, two times with saturated aqueous sodium bicarbonate, and once with saturated aqueous sodium chloride. The organic layer was collected and dried with Na2SO4. This mixture was then filtered, the filtrate was collected and concentrated and dried in-vacuo affording (R)-tert-Butyl 3-(2-aminophenylcarbamoyl)piperidine-1-carboxylate (7A) as a brownish foam that was carried directly on to the next step without further purification. ESI-MS: m/z 320.4 (M+H)+.

Workup

  1. customequipped
  2. stirringto stir for 5 min at room temperature
  3. stirringto stir at room temperature for 16 hr
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed three times with water, two times with saturated aqueous sodium bicarbonate
  6. customThe organic layer was collected
  7. dry with materialdried with Na2SO4
  8. filtrationThis mixture was then filtered
  9. customthe filtrate was collected
  10. concentrationconcentrated
  11. customdried in-vacuo

Sources & evidence

ORD record
ord-ae1621a44d0f44f7af9a8eee35260c12
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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