Ethyl dichloroacetate → HCID 59447468, compound

HRID 1518327Notes

Reaction equation

HRID 1518327 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][CH:11]=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl[CH:14](Cl)[C:15]([O:17][CH2:18][CH3:19])=[O:16].C([O-])C.[Na+].[S:25]1[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[N:27]=[C:26]1[NH:34][C:35]([C:37]1[CH:38]=[CH:39][CH:40]=[C:41]2[C:46]=1[CH2:45][N:44]([C:47](=[S:49])[NH2:48])[CH2:43][CH2:42]2)=[O:36]>CCOCC.CCO.CN(C=O)C>[S:25]1[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[N:27]=[C:26]1[NH:34][C:35]([C:37]1[CH:38]=[CH:39][CH:40]=[C:41]2[C:46]=1[CH2:45][N:44]([C:47]1[S:49][C:11]([CH2:10][CH2:9][O:8][Si:1]([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3])=[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[N:48]=1)[CH2:43][CH2:42]2)=[O:36]

Participants

8

Reactant 4

HCID 10808Ethyl dichloroacetateHCID 2723922Sodium ethoxideHCID 36623923-((Tert-butyldimethylsilyl)oxy)propanalHCID 59447545HCID 59447545, compound

Product 1

HCID 59447468HCID 59447468, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-(tert-butyldimethylsilyloxy)propanal (1 g, 5.31 mmol) and ethyl 2,2-dichloroacetate (0.651 mL, 5.31 mmol) in Et2O (4 mL) at 0° was dropwise added sodium ethanolate (0.397 g, 5.84 mmol) in EtOH (4 mL). The reaction mixture was stirred at 0° C. for 1.5 h and diluted with Et2O. The resulting mixture was washed with brine and the organic layer was dried over Na2SO4 and concentrated under reduced pressure. The residue was dried in vacuo and dissolved in EtOH (8 mL). To the resulting solution was added Example 49A (1 eq) in DMF. The reaction mixture was heated at 50° C. for 8 hours and concentrated under reduced pressure. The residue was dissolved in DCM and purified by column chromatography on silica gel eluting with 0% to 17% EtOAc in hexanes, then with 0% to 15% EtOAc in DCM to provide the desired product 49B: LCMS (APCI): m/z 623 (M+H).

Workup

  1. customat 0°
  2. washThe resulting mixture was washed with brine
  3. dry with materialthe organic layer was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was dried in vacuo
  6. dissolutiondissolved in EtOH (8 mL)
  7. temperatureThe reaction mixture was heated at 50° C. for 8 hours
  8. concentrationconcentrated under reduced pressure
  9. dissolutionThe residue was dissolved in DCM
  10. custompurified by column chromatography on silica gel eluting with 0% to 17% EtOAc in hexanes

Sources & evidence

ORD record
ord-c3ce687aca9c4fcba5c0644c7d9485fa
Source dataset
uspto-grants-2012_07
Patent number
US08232273B2

Reaction notes

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