Chloride → HCID 67463330, compound

HRID 2202796Notes

Reaction equation

HRID 2202796 reaction equation
Br[C:2]1[S:3][CH:4]=[C:5](Br)[N:6]=1.C([Li])CCC.[Cl-].[C:14]([O:18][C:19]([N:21]1[CH:26]2[CH2:27][CH2:28][CH:22]1[CH2:23][C:24](=[O:29])[CH2:25]2)=[O:20])([CH3:17])([CH3:16])[CH3:15].[Cl-].[NH4+]>C(OCC)C>[C:14]([O:18][C:19]([N:21]1[CH:26]2[CH2:27][CH2:28][CH:22]1[CH2:23][C:24]([OH:29])([C:5]1[N:6]=[CH:2][S:3][CH:4]=1)[CH2:25]2)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

7

Reactant 5

HCID 312ChlorideHCID 25517Ammonium ChlorideHCID 27632972,4-Dibromo-1,3-thiazoleHCID 2794767tert-Butyl 3-oxo-8-azabicyclo(3.2.1)octane-8-carboxylateHCID 178418339Butyllithium2×

Product 1

HCID 67463330HCID 67463330, compoundYield 17.7%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Procedure

2,4-dibromothiazole (1.1 g, 4.52 mmol) in diethyl ether (5 mL) was added to a solution of n-butyl lithium (2.5 M, 2 mL, 5 mmol) in diethyl ether (10 mL) at −78° C. and stirred for 0.5 hours. Trimethylsiliyl chloride (0.57 mL, 4.52 mmol) was added and the reaction mixture stirred for a further 0.5 hours before more n-butyl lithium (2.5M, 2 mL, 5 mmol) was added and stirred for 0.5 hours. 3-Oxo-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (0.9 g, 4 mmol) in diethyl ether (5 mL) was added and stirred for 0.5 hours before the reaction mixture was warmed to room temperature. Saturated aqueous ammonium chloride was added and the mixture extracted into ethyl acetate, dried over magnesium sulphate, filtered and the solvent removed by evaporation under vacuum. The residue was purified by flash chromatography on silica eluting with 20-30% ethyl acetate/cyclohexane. The fractions containing the desired product were concentrated under vacuum to give the title compound (0.22 g). LCMS m/z 311.3 [M+H]+. R.T.=3.05 min. (Analytical Method 3).

Workup

  1. additionwas added
  2. stirringstirred for 0.5 hours
  3. stirringstirred for 0.5 hours before the reaction mixture
  4. extractionthe mixture extracted into ethyl acetate
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. customthe solvent removed by evaporation under vacuum
  8. customThe residue was purified by flash chromatography on silica eluting with 20-30% ethyl acetate/cyclohexane
  9. additionThe fractions containing the desired product
  10. concentrationwere concentrated under vacuum

Sources & evidence

ORD record
ord-0261224f34ae4e9184ce81d1a97b7c33
Source dataset
uspto-grants-2016_06
Patent number
US09365564B2

Reaction notes

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