Sodium Iodide → N-(tert-butoxycarbonyl)piperidine

HRID 2111895Notes

Reaction equation

HRID 2111895 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11](NCC(C)C)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ClCC1N=CSC=1.[I-].[Na+].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 27632904-(Chloromethyl)-1,3-thiazoleHCID 15380699tert-Butyl 4-(isobutylamino)piperidine-1-carboxylate

Product 1

HCID 7010304N-(tert-butoxycarbonyl)piperidineYield 143.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-isobutylamino-piperidine-1-carboxylic acid tert-butyl ester (537 mg, 2.1 mmol, 1 eq.) and 4-chloromethyl-thiazole (280 mg, 2.10 mmol, 1 eq.) in anhydrous dimethylformamide (6 mL) is added sodium iodide (66 mg, 0.44 mmol, 0.2 eq.) and potassium carbonate (354 mg, 2.5 mmol, 1.2 eq.), the reaction mixture is stirred at room temperature for 3 days, and then water and ethyl acetate are added. The layers are separated, and the aqueous layer is extracted with ethyl acetate. The combined organics are dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude material is purified using medium pressure liquid chromatography eluting from 0 to 25% THF in hexanes to afford 4-}isobutyl-[(thiazol-4-yl)methyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester (559 mg, 75%). m/z=354 (M+1); 1H NMR (CDCl3): δ=8.68 (1H, brs), 7.16 (1H, brs), 4.11 (2H, brs), 3.80 (2H, brs), 2.58 (3H, brs), 2.25-2.22 (2H, m), 1.71-1.57 (3H, m), 1.46-1.32 (11H, m), 0.82 (6H, d).

Workup

  1. customThe layers are separated
  2. extractionthe aqueous layer is extracted with ethyl acetate
  3. dry with materialThe combined organics are dried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material is purified
  7. washeluting from 0 to 25% THF in hexanes

Sources & evidence

ORD record
ord-4815bdbabaa64c61a6405db55a99eb97
Source dataset
uspto-grants-2009_04
Patent number
US07521462B2

Reaction notes

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