4-Benzyloxyaniline hydrochloride → (4-Benzyloxy-phenyl)-(3-methyl-but-2-enyl)-[1-(3-methyl-butyl)-piperidin-4-yl]-amine

HRID 1069179Notes

Reaction equation

HRID 1069179 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.[CH2:30](OC1C=CC(N)=CC=1)[C:31]1[CH:36]=[CH:35]C=C[CH:32]=1.[C:45](N1CCC(=O)CC1=C=O)([CH3:48])([CH3:47])[CH3:46].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CCOC(C)=O.C(Cl)Cl>[CH2:22]([O:21][C:18]1[CH:19]=[CH:20][C:15]([N:14]([CH2:35][CH:36]=[C:31]([CH3:30])[CH3:32])[CH:11]2[CH2:10][CH2:9][N:8]([CH2:6][CH2:46][CH:45]([CH3:48])[CH3:47])[CH2:13][CH2:12]2)=[CH:16][CH:17]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 27238314-Benzyloxyaniline hydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 105479494-(4-Benzyloxy-phenylamino)-piperidine-1-carboxylic acid tert-butyl esterHCID 867570571-Tert-butyl-2-(oxomethylidene)piperidin-4-one

Product 1

HCID 9910060(4-Benzyloxy-phenyl)-(3-methyl-but-2-enyl)-[1-(3-methyl-butyl)-piperidin-4-yl]-amineYield 94%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

The preparation of 4-(4-Benzyloxy-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester (Ia): 4-Benzyloxyaniline hydrochloride salt (10 g, 42.4 mmol) was suspended in EtOAc (500 mL) and washed three times with saturated sodium bicarbonate solution, once with brine, dried over Na2SO4, and concentrated. The free base was dissolved in CH2Cl2 (250 mL), treated with 1-tert-butyl-carbonyl-4-piperidone (8.45 g, 42.4 mmol), stirred for thirty minutes and then cooled to 0° C. NaBH(OAc)3 (13.5 g, 63.6 mmol) was added and the reaction was allowed to warm to room temperature and stir for eighteen hours. The reaction was diluted with CH2Cl2 (250 mL), washed with saturated sodium bicarbonate solution and brine, dried over Na2SO4, and concentrated to give 15.3 g (94%) of the desired product. MS: 383 (M+1 for C23H30N2O3); TLC: SiO2, Rf0.39 (2:1 hexane/EtOAc).

Workup

  1. washwashed three times with saturated sodium bicarbonate solution
  2. dry with materialonce with brine, dried over Na2SO4
  3. concentrationconcentrated
  4. dissolutionThe free base was dissolved in CH2Cl2 (250 mL)
  5. temperatureto warm to room temperature
  6. stirringstir for eighteen hours
  7. washwashed with saturated sodium bicarbonate solution and brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-151f9911070142fca7d8da217c08cf13
Source dataset
uspto-grants-2001_06
Patent number
US06251919B1

Reaction notes

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