Hydrochloric Acid → 1-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acid

HRID 1827334Notes

Reaction equation

HRID 1827334 reaction equation
[NH:1]1[CH2:9][CH2:8][CH:4]([C:5]([OH:7])=[O:6])[CH2:3][CH2:2]1.C([O-])(O)=O.[Na+].[O:15](C(OC(C)(C)C)=O)[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=O.Cl>O1CCOCC1.O>[C:19]([O:18][C:16]([N:1]1[CH2:9][CH2:8][CH:4]([C:5]([OH:7])=[O:6])[CH2:3][CH2:2]1)=[O:15])([CH3:22])([CH3:21])[CH3:20]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 37734-Piperidinecarboxylic acidHCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium Bicarbonate

Product 1

HCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidYield 91%

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

A solution of isonipecotic acid (18) (2.6 g, 20 mmol) in 1,4-dioxane/H2O (3:2, 100 mL) was treated with NaHCO3 (8.4 g, 100 mmol, 20 mL H2O), followed by t-Boc2O (4.8 g, 22 mmol) at room temperature. After stirring for 3 h, the solution was acidified with 1 N HCl (50 mL), extracted with EtOAc (3×100 mL). The combined organic extracts were washed with saturated solution of NaHCO3 (50 mL), brine (50 mL), dried over MgSO4 and concentrated to give a white solid (19) (4.16 g, 91%). 1H NMR (500 MHz, CDCl3) δ 4.02 (br s, 2H), 2.86 (t, J=12.0 Hz, 2H), 2.50 (tt, J=11.0, 4.0 Hz, 1H), 1.91 (dd, J=13.0, 2.5 Hz, 2H), 1.65 (m, 2H), 1.46 (s, 9H), MS (ESI−) m/z 228.65 (M−H−).

Workup

  1. extractionextracted with EtOAc (3×100 mL)
  2. washThe combined organic extracts were washed with saturated solution of NaHCO3 (50 mL), brine (50 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-58f8e2178e5a45f9813a00b0219ce1f5
Source dataset
uspto-grants-2006_05
Patent number
US07053214B2

Reaction notes

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