Lithium diisopropylamide → HCID 86729199, compound

HRID 539560Notes

Reaction equation

HRID 539560 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[C:14]([CH3:19])[CH:13]=2)=[O:11])[CH:5]=[C:6]([F:8])[CH:7]=1.C([N-]C(C)C)(C)C.[Li+].Br[CH2:29][CH2:30][CH2:31][S:32][C:33]1[CH:42]=[CH:41][C:36]([C:37]([O:39][CH3:40])=[O:38])=[CH:35][CH:34]=1>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:9]([C:10]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[C:14]([CH3:19])[CH:13]=2)=[O:11])[CH2:29][CH2:30][CH2:31][S:32][C:33]2[CH:42]=[CH:41][C:36]([C:37]([O:39][CH3:40])=[O:38])=[CH:35][CH:34]=2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 19907415HCID 19907415, compoundHCID 62548345HCID 62548345, compound

Product 1

HCID 86729199HCID 86729199, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A sample of 2-(3,5-difluorophenyl)-1-(3,4-dimethylphenyl)ethanone [CAS 1450736-61-4] (5.0 g, 19.2 mmole) was dissolved in THF and cooled to −78° C. Lithium diisopropyl amide (10.6 mL, 1.1 eq.) was added dropwise and the resulting mixture was stirred for 30 minutes. A solution of methyl 4-[(3-bromopropyl)thio]benzoate [CAS 134520-57-3] (6.1 g, 1.1 eq) in THF was then added dropwise and the reaction mixture was allowed to stir overnight. It was then refluxed at 90° C. overnight. The reaction mixture was cooled to room temperature, then to 0° C. after which it was quenched with 1M HCl to pH 2. The resulting mixture was extracted with EtOAc (3×100 mL) and the combined organic layers were washed with saturated NaCl, dried with MgSO4, filtered, concentrated and purified by MPLC to give 4.28 g (48%) of Intermediate

Workup

  1. stirringto stir overnight
  2. temperatureIt was then refluxed at 90° C. overnight
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customto 0° C. after which it was quenched with 1M HCl to pH 2
  5. extractionThe resulting mixture was extracted with EtOAc (3×100 mL)
  6. washthe combined organic layers were washed with saturated NaCl
  7. dry with materialdried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by MPLC

Sources & evidence

ORD record
ord-075b29822eab4ae4884e45ac02cbe902
Source dataset
uspto-grants-2014_10
Patent number
US08871755B2

Reaction notes

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