Tetrahydrofuran → HCID 69148085, compound

HRID 2114812Notes

Reaction equation

HRID 2114812 reaction equation
[O:1]=[C:2]1[NH:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1.[Cl:30][C:31]1[CH:32]=[C:33]([CH:36]=[CH:37][C:38]=1[F:39])[CH2:34]Br>CN(C=O)C>[Cl:30][C:31]1[CH:32]=[C:33]([CH:36]=[CH:37][C:38]=1[F:39])[CH2:34][N:7]1[CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3][C:2]1=[O:1]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 2733832Lithium HexamethyldisilazideHCID 27575424-(Bromomethyl)-2-chloro-1-fluorobenzeneHCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylate

Product 1

HCID 69148085HCID 69148085, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cold (0° C.) suspension of tert-butyl 3-oxopiperazine-1-carboxylate (2.0 g, 9.99 mmol) in DMF (20 mL) under an atmosphere of nitrogen, a solution of lithium bis(trimethylsilyl)amide in THF (10.69 mL, 10.69 mmol) was added and stirred at the temperature for 30 min. The resultant clear red brown solution was treated with 3-chloro-4-fluorobenzyl bromide (2.34 mL, 10.49 mmol), and stirred at 0° C. for 2 hours. The product mixture was concentrated under vacuum, and the residue partitioned between water and ethyl acetate. The organic extract was washed successively with 5% aq KHSO4, sat. NaHCO3, and brine. The organic fraction was dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with a 0-100% gradient of ethyl acetate in hexane. Collection and concentration of appropriate fractions provided the benzylated product.

Workup

  1. stirringstirred at 0° C. for 2 hours
  2. concentrationThe product mixture was concentrated under vacuum
  3. customthe residue partitioned between water and ethyl acetate
  4. extractionThe organic extract
  5. washwas washed successively with 5% aq KHSO4, sat. NaHCO3, and brine
  6. dry with materialThe organic fraction was dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customCollection and concentration of appropriate fractions
  10. customprovided the benzylated product

Sources & evidence

ORD record
ord-85db0b7a787f46938ac173a7903a3e8d
Source dataset
uspto-grants-2008_10
Patent number
US07435735B2

Reaction notes

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