Citric Acid → HCID 90060310, compound

HRID 1779259Notes

Reaction equation

HRID 1779259 reaction equation
C([Si](C)(C)[O:6][CH2:7][CH2:8][C@:9]([OH:55])([C@@H:17]([C:38](=[O:54])[NH:39][C@H:40]([C:49]([O:51][CH2:52][CH3:53])=[O:50])[CH2:41][C:42]1[CH:47]=[CH:46][C:45]([OH:48])=[CH:44][CH:43]=1)/[CH:18]=[CH:19]/[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]1([CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])OCC[O:27]1)[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])(C)(C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(=O)([O-])[O-].[K+].[K+].Br[CH2:78][C:79]#[C:80][CH3:81]>C(#N)C.CN(C=O)C.O>[CH2:78]([O:48][C:45]1[CH:44]=[CH:43][C:42]([CH2:41][C@H:40]([NH:39][C:38]([C@@H:17](/[CH:18]=[CH:19]/[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26](=[O:27])[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[C@@:9]([OH:55])([CH2:8][CH2:7][OH:6])[C:10]([O:12][C:13]([CH3:15])([CH3:16])[CH3:14])=[O:11])=[O:54])[C:49]([O:51][CH2:52][CH3:53])=[O:50])=[CH:47][CH:46]=1)[C:79]#[C:80][CH3:81]

Participants

8

Reactant 4

HCID 311Citric AcidHCID 11430Potassium CarbonateHCID 27568621-Bromo-2-butyneHCID 90060435HCID 90060435, compound

Product 1

HCID 90060310HCID 90060310, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

tert-Butyl (E)-(2S,3S)-2-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-3-[(S)-1-ethoxycarbonyl-2-(4-hydroxy-phenyl)-ethylcarbamoyl]-11-(2-heptyl-[1,3]dioxolan-2-yl)-2-hydroxy-undec-4-enoate (909 mg) was dissolved in acetonitrile (9.0 mL), and an aqueous solution (3.6 mL) of 0.5 M citric acid was added. The mixture was stirred at 60° C. for 3 hours. Water was then added to the reaction mixture, which was followed by extraction with a mixed solvent of ethyl acetate/n-hexane. The organic extract was dried over magnesium sulfate, and concentrated under reduced pressure to obtain a crude product (660 mg). The obtained crude product (182 mg) was dissolved in DMF, and potassium carbonate (49.4 mg) and 1-bromo-but-2-yne (28.9 μL) were added. The mixture was stirred at room temperature for 20 hours. Water was then added to the reaction mixture, which was followed by extraction with a mixed solvent of ethyl acetate/n-hexane. The organic layer was washed with a saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (74 mg).

Workup

  1. extractionwas followed by extraction with a mixed solvent of ethyl acetate/n-hexane
  2. extractionThe organic extract
  3. dry with materialwas dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customto obtain a crude product (660 mg)
  6. customThe obtained crude product (182 mg)
  7. stirringThe mixture was stirred at room temperature for 20 hours
  8. extractionwas followed by extraction with a mixed solvent of ethyl acetate/n-hexane
  9. washThe organic layer was washed with a saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-80d9454350414256a5b096e9b19c1bb8
Source dataset
uspto-grants-2016_02
Patent number
US09266853B2

Reaction notes

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