Tert-Butyl nitrite → 4-(4-Ethoxycarbonyl-thiophen-2-yl)-piperidine-1-carboxylic acid t-butyl ester

HRID 1809058Notes

Reaction equation

HRID 1809058 reaction equation
C([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[S:15][C:16](N)=[C:17]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:18]=2)[CH2:10][CH2:9]1)=O)CCC.N([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=O>[Cu](Cl)Cl.[Cl-].[NH4+]>[C:28]([O:27][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14]2[S:15][CH:16]=[C:17]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:18]=2)[CH2:12][CH2:13]1)=[O:5])([CH3:31])([CH3:30])[CH3:29]

Participants

5

Reactant 2

HCID 10906Tert-Butyl nitriteHCID 687350294-(5-Amino-4-ethoxycarbonyl-thiophen-2-yl)-piperidine-1-carboxylic acid butyl ester

Product 1

HCID 595425854-(4-Ethoxycarbonyl-thiophen-2-yl)-piperidine-1-carboxylic acid t-butyl esterYield 90.7%

Reagents, catalysts & solvents 2

HCID 24014Cupric ChlorideCatalystHCID 25517Ammonium ChlorideSolvent

Procedure

4-(5-Amino-4-ethoxycarbonyl-thiophen-2-yl)-piperidine-1-carboxylic acid butyl ester (13.4 g, 38 mmol) was added to t-butyl nitrite (56.4 mmol) and copper(II)chloride (38 mmol) in IMS (500 mL). The reaction was stirred for 1 hour then saturated aqueous ammonium chloride (70 mL) was added and the resulting mixture stirred for a further 15 minutes. The solution was filtered and the filtrate was evaporated under vacuum. The residue was then partitioned between DCM and water. The organic layer was separated and dried over magnesium sulphate, filtered and the solvent evaporated. The product was purified by column chromatography on silica, eluting with 0%-40% ethyl acetate in cyclohexane to give a clear oil (11.7 g). 1H NMR (400 MHz, CHCl3-d): δ 7.9 (s, 1H), 7.2 (s, 1H), 4.3 (q, 2H), 4.2 (m, 2H), 2.9-2.7 (m, 3H), 2.0 (m, 2H), 1.7 (m, 2H), 1.5 (s, 9H), 1.4 (t, 3H).

Workup

  1. stirringthe resulting mixture stirred for a further 15 minutes
  2. filtrationThe solution was filtered
  3. customthe filtrate was evaporated under vacuum
  4. customThe residue was then partitioned between DCM and water
  5. customThe organic layer was separated
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered
  8. customthe solvent evaporated
  9. customThe product was purified by column chromatography on silica
  10. washeluting with 0%-40% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-4d8d7de0e60348588453813079f58e70
Source dataset
uspto-grants-2013_01
Patent number
US08362008B2

Reaction notes

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