Acetic Acid → HCID 69141315, compound

HRID 1794150Notes

Reaction equation

HRID 1794150 reaction equation
[F:1][C:2]1[CH:26]=[CH:25][C:24](I)=[CH:23][C:3]=1[CH2:4][O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][C@H:9]1[CH2:21][CH3:22])=[O:7].C([Li])CCC.C(O)(=[O:35])C.OO>O1CCCC1>[F:1][C:2]1[CH:26]=[CH:25][C:24]([OH:35])=[CH:23][C:3]=1[CH2:4][O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][C@H:9]1[CH2:21][CH3:22])=[O:7]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 784Hydrogen PeroxideHCID 69144021HCID 69144021, compoundHCID 178418339Butyllithium

Product 1

HCID 69141315HCID 69141315, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

(R)-2-Ethyl-piperazine-1,4-dicarboxylic acid 4-tert-butyl ester 1-(2-fluoro-5-iodo-benzyl) ester (8.9 g, 18 mM) was dissolved in tetrahydrofuran (150 mL), trisopropylborate (6.7 g, 36 mM) was added and the mixture was cooled to −78° C. At this low temperature n-butyllithium (16.9 mL, 1.6N) was added drop by drop with stirring. The mixture was stirred for 45 min at −78° C., for another 45 min at −50° C. and for 15 min at 0° C. Acetic acid (9.5 mL, 50%) was added slowly with stirring (0–5° C.), followed by hydrogen peroxide (2.75 mL, 35%). Stirring continued with cooling for another 45 min and for 1 h at room temperature. The mixture was partitioned between water and diethylether, organic phases were pooled, washed with water, sodium thiosulfate solution (5%), brine and dried with Na2SO4 to yield after evaporation a light yellow oil (8.5 g). This residue was purified by column chromatography (silica gel; n-hexane/ethylacetate 1:1) to yield 3.0 g (43%) of the product as a yellowish oil. MS (ISP): 400.5 (M+NH4)+.

Workup

  1. additiontrisopropylborate (6.7 g, 36 mM) was added
  2. stirringThe mixture was stirred for 45 min at −78° C., for another 45 min at −50° C. and for 15 min at 0° C
  3. stirringwith stirring (0–5° C.)
  4. stirringStirring
  5. temperaturewith cooling for another 45 min and for 1 h at room temperature
  6. customThe mixture was partitioned between water and diethylether, organic phases
  7. washwashed with water, sodium thiosulfate solution (5%), brine
  8. dry with materialdried with Na2SO4
  9. customto yield
  10. customafter evaporation a light yellow oil (8.5 g)
  11. customThis residue was purified by column chromatography (silica gel; n-hexane/ethylacetate 1:1)

Sources & evidence

ORD record
ord-907f16b1c3234d4892d3a30c594cd63e
Source dataset
uspto-grants-2006_04
Patent number
US07022707B2

Reaction notes

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