Imidazole → 7-{2-[2-(tert-Butyldimethylsilanyloxy)ethoxymethyl]thiazol-5-yl}-3,9-diazabicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic acid 3,9-di-tert-butyl ester

HRID 1096845Notes

Reaction equation

HRID 1096845 reaction equation
[CH3:1][C:2]([Si:5](Cl)([CH3:7])[CH3:6])([CH3:4])[CH3:3].N1C=CN=C1.[C:14]([O:18][C:19]([N:21]1[CH2:28][CH:27]2[N:29]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH:23]([CH2:24][C:25]([C:40]3[S:44][C:43]([CH2:45][O:46][CH2:47][CH2:48][OH:49])=[N:42][CH:41]=3)=[C:26]2[C:37]([OH:39])=[O:38])[CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].C([O-])([O-])=O.[K+].[K+]>C1COCC1.O.CO>[C:14]([O:18][C:19]([N:21]1[CH2:28][CH:27]2[N:29]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH:23]([CH2:24][C:25]([C:40]3[S:44][C:43]([CH2:45][O:46][CH2:47][CH2:48][O:49][Si:5]([C:2]([CH3:4])([CH3:3])[CH3:1])([CH3:7])[CH3:6])=[N:42][CH:41]=3)=[C:26]2[C:37]([OH:39])=[O:38])[CH2:22]1)=[O:20])([CH3:15])([CH3:16])[CH3:17]

Participants

8

Reactant 4

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 28928tert-Butyldimethylsilyl chlorideHCID 866370687-[2-(2-Hydroxyethoxymethyl)thiazol-5-yl]-3,9-diazabicyclo[3.3.1]-non-6-ene-3,6,9-tricarboxylic acid 3,9-di-tert-butyl ester

Product 1

HCID 685735637-{2-[2-(tert-Butyldimethylsilanyloxy)ethoxymethyl]thiazol-5-yl}-3,9-diazabicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic acid 3,9-di-tert-butyl esterYield 108.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

TBDMS-Cl (184 mg, 1.22 mmol), and imidazole (131 mg, 1.95 mmol) were added to a stirred solution of the compound D7 (256 mg, 0.488 mmol) in THF (2.5 mL). The reaction mixture was stirred at rt for 15 h. The crude mixture was partitioned between Et2O and aq. sat. NH4Cl. The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. The crude oil was dissolved in THF (4.5 mL), MeOH (0.7 mL), and water (0.7 mL), and K2CO3 (34 mg, 0.024 mmol) was added. The mixture was stirred at rt for 3 h. The mixture was partitioned between Et2O and aq. sat. NH4Cl, and the aq. layer was extracted once more with Et2O. The combined org. extracts were dried over MgSO4, filtered, and the solvents were removed in vacuo to yield the title compound (0.34 g, quantitative yield) as a yellow oil that was not further purified. LC-MS: tR=1.10 min, ES+: 640.50.

Workup

  1. customThe crude mixture was partitioned between Et2O and aq. sat. NH4Cl
  2. dry with materiallayer was dried over MgSO4
  3. filtrationfiltered
  4. customthe solvents were removed under reduced pressure
  5. dissolutionThe crude oil was dissolved in THF (4.5 mL)
  6. stirringThe mixture was stirred at rt for 3 h
  7. customThe mixture was partitioned between Et2O and aq. sat. NH4Cl
  8. extractionthe aq. layer was extracted once more with Et2O
  9. dry with materialextracts were dried over MgSO4
  10. filtrationfiltered
  11. customthe solvents were removed in vacuo

Sources & evidence

ORD record
ord-5665bf3275864a12b5b6fdfd9c4694a4
Source dataset
uspto-grants-2012_03
Patent number
US08138340B2

Reaction notes

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