Diisopropylamine → HCID 58825030, compound

HRID 270935Notes

Reaction equation

HRID 270935 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][O:14][C:15](=[O:24])[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][CH:18]=1.[CH:25]1([C:31](Cl)=[O:32])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1>O1CCCC1.CCCCCC>[CH3:13][O:14][C:15](=[O:24])[CH:16]([C:17]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][CH:18]=1)[C:31]([CH:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1)=[O:32]

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 75938Cyclohexanecarbonyl chlorideHCID 10378700Methyl 4-IodophenylacetateHCID 178418339Butyllithium

Product 1

HCID 58825030HCID 58825030, compoundYield 80.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 2.88 mL (20.5 mmol) of diisopropylamine (iPr2NH) in 50 mL of tetrahydrofuran (THF) was flushed with argon and cooled to −78° C. To this solution was added dropwise 8.2 mL (20.5 mmol) of n-butyllithium (nBuLi) 2.5 M solution in hexane, and the resulting mixture was stirred at −78° C. for 20 min, after which time a solution of 4.5 g (16.3 mmol) of (4-iodo-phenyl)-acetic acid methyl ester in 25 mL of THF was added dropwise. The mixture was allowed to warm up to rt for 40 min, then it was cooled again to −78° C., and 2.62 mL (19.6 mmol) of cyclohexanecarbonyl chloride was added dropwise, and the resulting mixture was allowed to warm up to rt, and stirred at rt overnight under argon. The reaction mixture was quenched on ice by the addition of saturated ammonium chloride solution, and extracted with ethyl acetate. The combined organic extracts were washed with water, brine, dried over sodium sulfate and concentrated to give 7 g of a burgundy oil which was chromatographed on silica gel (Biotage; 10% ethyl acetate in hexane) to afford 5.06 g (80% yield) of desired 3-cyclohexyl-2-(4-iodo-phenyl)-3-oxo-propionic acid methyl ester as a pale yellow solid as indicated by 1H NMR (1:2.6 keto: enol ratio). LC-MS—calcd for C16H19IO3 [M++H]+: 387.04, found: 387.0.

Workup

  1. temperatureto warm up to rt for 40 min
  2. temperatureit was cooled again to −78° C.
  3. temperatureto warm up to rt
  4. stirringstirred at rt overnight under argon
  5. customThe reaction mixture was quenched on ice by the addition of saturated ammonium chloride solution
  6. extractionextracted with ethyl acetate
  7. washThe combined organic extracts were washed with water, brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customto give 7 g of a burgundy oil which
  11. customwas chromatographed on silica gel (Biotage; 10% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-c880907a1d2f4bd1bd419b554ff6d1eb
Source dataset
uspto-grants-2008_11
Patent number
US07449488B2

Reaction notes

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