Acetic Acid → Acetic Acid

HRID 1487312Notes

Reaction equation

HRID 1487312 reaction equation
[CH2:1]([C@H:3]1[C@H:8]([NH:9][C@@H](C2C=CC=CC=2)C)[CH2:7][CH2:6][N:5]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:4]1)[CH3:2].[C:25]([OH:28])(=[O:27])[CH3:26]>[OH-].[OH-].[Pd+2]>[NH2:9][C@@H:8]1[CH2:7][CH2:6][N:5]([C:18]([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:19])[CH2:4][C@H:3]1[CH2:1][CH3:2].[CH3:26][C:25]([OH:28])=[O:27]

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 68350379(3R,4R)-tert-butyl 3-ethyl-4-(((R)-1-phenylethyl)amino)piperidine-1-carboxylate

Product 2

HCID 176Acetic AcidYield 94%HCID 68291633(3R,4R)-tert-butyl 4-amino-3-ethylpiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 9942167Palladium hydroxideCatalyst

Procedure

A flask was flushed with nitrogen and charged with 20% palladium hydroxide on carbon (91 mg, 0.647 mmol). A solution of (3R,4R)-tert-butyl 3-ethyl-4-(((R)-1-phenylethyl)amino)piperidine-1-carboxylate (430.5 mg, 1.295 mmol) in acetic acid (8.6 ml) was added. The flask was flushed with nitrogen, sealed, evacuated briefly, and charged with hydrogen. The mixture was stirred at room temperature for 14 hrs. The flask was evacuated, backfilled with nitrogen, and opened. The reaction mixture is filtered through CELITE®. The filtrate was concentrated by azeotropical distillation with toluene (3×25 ml) under reduced pressure to remove the residual acetic acid, yielding (3R,4R)-tert-Butyl 4-amino-3-ethylpiperidine-1-carboxylate, HOAc salt (351 mg, 1.217 mmol, 94.0% yield) as a white solid. 1H NMR (400 MHz, methanol-d4) δ 4.16 (d, J=11.2 Hz, 1H), 4.07 (d, J=13.9 Hz, 1H), 3.03-2.85 (m, 2H), 2.56 (br. s., 1H), 2.02-1.94 (m, 1H), 1.92 (s, 3H), 1.77-1.66 (m, 1H), 1.53-1.36 (m, 10H), 1.32-1.16 (m, 1H), 1.00 (t, J=7.5 Hz, 3H).

Workup

  1. customA flask was flushed with nitrogen
  2. customThe flask was flushed with nitrogen
  3. customsealed
  4. customevacuated briefly
  5. additioncharged with hydrogen
  6. customThe flask was evacuated
  7. filtrationThe reaction mixture is filtered through CELITE®
  8. concentrationThe filtrate was concentrated by azeotropical distillation with toluene (3×25 ml) under reduced pressure
  9. customto remove the residual acetic acid

Sources & evidence

ORD record
ord-68c9d7a302b1409a9af786dafe8396d5
Source dataset
uspto-grants-2016_08
Patent number
US09428511B2

Reaction notes

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