Lithium diisopropylamide → 3-(4-Bromo-2-chloro-benzyl)-1-(4,4-difluoro-cyclohexyl)-pyrrolidin-2-one

HRID 1672742Notes

Reaction equation

HRID 1672742 reaction equation
[F:1][C:2]1([F:14])[CH2:7][CH2:6][CH:5]([N:8]2[CH2:12][CH2:11][CH2:10][C:9]2=[O:13])[CH2:4][CH2:3]1.[Li+].CC([N-]C(C)C)C.[Br:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30]Br)=[C:26]([Cl:32])[CH:25]=1>C1COCC1.CCCCCC>[Br:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][CH:10]2[CH2:11][CH2:12][N:8]([CH:5]3[CH2:4][CH2:3][C:2]([F:1])([F:14])[CH2:7][CH2:6]3)[C:9]2=[O:13])=[C:26]([Cl:32])[CH:25]=1

Participants

6

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 219144864-Bromo-1-(bromomethyl)-2-chlorobenzeneHCID 57878591HCID 57878591, compound

Product 1

HCID 578786043-(4-Bromo-2-chloro-benzyl)-1-(4,4-difluoro-cyclohexyl)-pyrrolidin-2-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

To a solution of 1-(4,4-difluoro-cyclohexyl)-pyrrolidin-2-one (190 mg, 0.94 mmol) in 10 mL dry THF, add 1.04 mL of 1.5M LDA (1.5 eq.) in hexane dropwise at −78° C. Then, add 0.59 g of 4-bromo-1-bromomethyl-2-chloro-benzene (1.5 eq) at −78° C. Allow the resulting solution to stand at room temp for overnight. Quench the mixture with saturated aqueous NaCl and extract with Et2O. Wash the organic layer with water, then brine, and dry over Na2SO4, filter and concentrate. Purify the crude material by chromatography to afford the title compound: mass spectrum (m/z): 407 (M+1).

Workup

  1. customQuench the mixture with saturated aqueous NaCl
  2. extractionextract with Et2O
  3. washWash the organic layer with water
  4. dry with materialbrine, and dry over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify the crude material by chromatography

Sources & evidence

ORD record
ord-11eb263ef19c4f67b46367a0fa0016c0
Source dataset
uspto-grants-2011_08
Patent number
US07998999B2

Reaction notes

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