tert-Butyl carbazate → 2-Isopropyl-4-((N-(tert-butyloxycarbonylamino)amino)methyl)thiazole

HRID 1858486Notes

Reaction equation

HRID 1858486 reaction equation
[C:1]([O:5][C:6](=[O:9])[NH:7][NH2:8])([CH3:4])([CH3:3])[CH3:2].Cl.Cl[CH2:12][C:13]1[N:14]=[C:15]([CH:18]([CH3:20])[CH3:19])[S:16][CH:17]=1>C(O)(C)C>[CH:18]([C:15]1[S:16][CH:17]=[C:13]([CH2:12][NH:8][NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:9])[N:14]=1)([CH3:20])[CH3:19]

Participants

4

Reactant 2

HCID 70091tert-Butyl carbazateHCID 187588464-(Chloromethyl)-2-(propan-2-yl)-1,3-thiazole--hydrogen chloride (1/1)

Product 1

HCID 187588582-Isopropyl-4-((N-(tert-butyloxycarbonylamino)amino)methyl)thiazole

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent2×

Procedure

A solution of 7.5 g (57 mmol) to t-butylcarbazate in 200 ml of isopropyl alcohol was treated with a solution of 1.0 g (57 mmol) of 4-(chloromethyl)-2-isopropylthiazole hydrochloride in 10 ml of isopropyl alcohol. The resulting solution was heated at reflux for 16 h, allowed to cool, and concentrated in vacuo. The residue was diluted with 1 N HCl, washed with three portions of ethyl acetate, basified to pH 12 with aqueous NaOH, and extracted with three portion of ethyl acetate. The combined organic layers were dried over MgSO4 and concentrated in vacuo. Purification of the residue by silica gel chromatography using 20% ethyl acetate in hexane provided 0.32 g (21%) of the desired compound (Rf 0.4, 5% methanol in chloroform). 1H NMR (CDCl3) δ 1.40 (d, J=7 Hz, 6 H), 1.47 (s, 9 H), 2.53 (br, 1 H), 3.33 (heptet, J=7 Hz, 1 H), 4.11 (s, 2 H), 6.22 (br, 1 H), 7.01 (s, 1 H). Mass spectrum: (M+H)+ =272.

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureat reflux for 16 h
  3. temperatureto cool
  4. concentrationconcentrated in vacuo
  5. additionThe residue was diluted with 1 N HCl
  6. washwashed with three portions of ethyl acetate
  7. extractionextracted with three portion of ethyl acetate
  8. dry with materialThe combined organic layers were dried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customPurification of the residue by silica gel chromatography

Sources & evidence

ORD record
ord-a04ff4482c0b4bf6ace6c9970ad9c66f
Source dataset
uspto-grants-2000_11
Patent number
US06150530

Reaction notes

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