Acetic Acid → 4-{Isobutyl-[(quinolin-3-yl)methyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 2111890Notes

Reaction equation

HRID 2111890 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([NH:28][CH2:29][CH:30]([CH3:32])[CH3:31])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].[N:33]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH:36]=[C:35]([CH:43]=O)[CH:34]=1.C(O)(=O)C.[OH-].[Na+]>ClCCCl>[C:15]([O:19][C:20]([N:22]1[CH2:23][CH2:24][CH:25]([N:28]([CH2:29][CH:30]([CH3:32])[CH3:31])[CH2:43][C:35]2[CH:34]=[N:33][C:42]3[C:37]([CH:36]=2)=[CH:38][CH:39]=[CH:40][CH:41]=3)[CH2:26][CH2:27]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 836413-QuinolinecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 15380699tert-Butyl 4-(isobutylamino)piperidine-1-carboxylate

Product 1

HCID 685745204-{Isobutyl-[(quinolin-3-yl)methyl]-amino}-piperidine-1-carboxylic acid tert-butyl esterYield 60%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Sodium triacetoxyborohydride (1.29 g, 6.09 mmol) is added to a stirred solution of 4-isobutylamino-piperidine-1-carboxylic acid tert-butyl ester (1.09 g, 4.29 mmol), quinoline-3-carboxaldehyde (0.68 g, 4.3 mmol), acetic acid (0.25 ml, 4.37 mmol), and 1,2-dichloroethane (15 ml). The reaction is stirred for 18 h at room temperature under nitrogen. The reaction is poured into 2N NaOH (100 ml) and extracted with ethyl acetate (100 ml×3). The ethyl acetate is dried over sodium sulfate and then the sodium sulfate is filtered off. The crude product is concentrated on a rotary evaporator and purified by flash chromatography on silica gel eluting with 15% acetone/hexanes to yield (1.02 g, 60%) of 4-{isobutyl-[(quinolin-3-yl)methyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester: mass spectrum (ion spray): m/z=398.2 (M+1); 1H NMR (CDCl3): δ=8.93 (1H, d), 8.09 (1H, d), 8.02 (1H, s), 7.79 (1H, d), 7.70-7.66 (1H, m), 7.55-7.51 (1H, m), 4.16 (2H, br s), 3.79 (2H, s), 2.63-2.57 (3H, m), 2.27 (2H, d), 1.77-1.65 (3H, m), 1.52-1.48 (2H, m), 1.44 (9H, s), 0.85 (6H, d).

Workup

  1. extractionextracted with ethyl acetate (100 ml×3)
  2. dry with materialThe ethyl acetate is dried over sodium sulfate
  3. filtrationthe sodium sulfate is filtered off
  4. concentrationThe crude product is concentrated on a rotary evaporator
  5. custompurified by flash chromatography on silica gel eluting with 15% acetone/hexanes

Sources & evidence

ORD record
ord-0c8f12f0b6744461b3e7cac23d2a3d5c
Source dataset
uspto-grants-2009_04
Patent number
US07521462B2

Reaction notes

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