Acetic Acid → tert-Butyl 4-(isobutylamino)piperidine-1-carboxylate

HRID 2111889Notes

Reaction equation

HRID 2111889 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O=[C:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1.[CH2:29]([NH2:33])[CH:30]([CH3:32])[CH3:31].C(O)(=O)C.[OH-].[Na+]>ClCCCl>[C:25]([O:24][C:22]([N:19]1[CH2:20][CH2:21][CH:16]([NH:33][CH2:29][CH:30]([CH3:32])[CH3:31])[CH2:17][CH2:18]1)=[O:23])([CH3:28])([CH3:27])[CH3:26]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 6558IsobutylamineHCID 14798Sodium HydroxideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 15380699tert-Butyl 4-(isobutylamino)piperidine-1-carboxylateYield 95.2%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Sodium triacetoxyborohydride (32.0 g, 151.0 mmol) is added to a stirred solution of tert-butyl 4-oxo-1-piperidine carboxylate (20.0 g, 100.4 mmol), isobutylamine (10.5 ml, 105.7 mmol), acetic acid (6.0 ml, 104.8 mmol) and 1,2-dichloroethane (300 ml). The reaction is stirred for 18 hours at room temperature under nitrogen. The reaction is poured into 2N NaOH (300 ml) and extracted with ethyl acetate (200 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 0.5% concentrated ammonium hydroxide/5% ethanol/chloroform to yield (24.5 g, 95%) of 4-isobutylamino-piperidine-1-carboxylic acid tert-butyl ester: mass spectrum (ion spray): m/z=257.1 (M+1); 1H NMR (CDCl3): δ=4.01 (2H, br s), 2.78-2.75 (2H, m), 2.60-2.53 (1H, m), 2.42 (2H, d), 1.83-1.64 (3H, m), 1.56 (1H, br s), 1.44 (9H, s), 1.28-1.18 (2H, m), 0.90 (6H, d).

Workup

  1. extractionextracted with ethyl acetate (200 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 0.5% concentrated ammonium hydroxide/5% ethanol/chloroform

Sources & evidence

ORD record
ord-427d8700998f40f6a032292ae119c960
Source dataset
uspto-grants-2009_04
Patent number
US07521462B2

Reaction notes

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