Imidazole → tert-butyl N-[(4RS)-4-(1-imidazolylmethyl)-4,5-dihydro-2-thiazolyl]carbamate

HRID 47767Notes

Reaction equation

HRID 47767 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[H-].[Na+].C1(C)C=CC(S(O[CH2:18][CH:19]2[CH2:23][S:22][C:21]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[N:20]2)(=O)=O)=CC=1>CN(C)C=O.C(OCC)(=O)C>[NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:18][CH:19]1[CH2:23][S:22][C:21]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[N:20]1

Participants

6

Reactant 3

HCID 795ImidazoleHCID 24758Sodium hydride2×HCID 22747841tert-butyl N-[(4RS)-4-(p-toluenesulfonyloxymethyl)-4,5-dihydro-2-thiazolyl]carbamate

Product 1

HCID 69885644tert-butyl N-[(4RS)-4-(1-imidazolylmethyl)-4,5-dihydro-2-thiazolyl]carbamateYield 34.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

0.21 g of imidazole predissolved in 10 cm3 of dimethylformamide is added to a solution of 0.085 g of sodium hydride in 20 cm3 of dimethylformamide. After the sodium hydride has disappeared, a solution of 1 g of tert-butyl N-[(4RS)-4-(p-toluenesulfonyloxymethyl)-4,5-dihydro-2-thiazolyl]carbamate in 10 cm3 of dimethylformamide is added and the mixture is then stirred at a temperature in the region of 70° C. for 3 hours. The reaction medium is diluted with ethyl acetate, washed with water, dried over magnesium sulfate and then concentrated under reduced pressure (1 kPa) at a temperature in the region of 40° C. The residue obtained is chromatographed on a column of alumina, eluting with ethyl acetate and a mixture of ethyl acetate/methanol (80/20 by volume). The fractions containing the expected product are combined and then concentrated under the above conditions to give 0.25 g of tert-butyl N-[(4RS)-4-(1-imidazolylmethyl)-4,5-dihydro-2-thiazolyl]carbamate in the form of a sticky yellow mass [mass spectrum: DCI m/z=283 MH+ m/z=183 (M-C5H7O2)+].

Workup

  1. washwashed with water
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated under reduced pressure (1 kPa) at a temperature in the region of 40° C
  4. customThe residue obtained
  5. customis chromatographed on a column of alumina
  6. washeluting with ethyl acetate
  7. additiona mixture of ethyl acetate/methanol (80/20 by volume)
  8. additionThe fractions containing the expected product
  9. concentrationconcentrated under the above conditions

Sources & evidence

ORD record
ord-b4148a701d624bba864b96983b5f80f3
Source dataset
uspto-grants-2004_03
Patent number
US06699895B2

Reaction notes

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