Lithium Hexamethyldisilazide → HCID 11638332, compound

HRID 735236Notes

Reaction equation

HRID 735236 reaction equation
CO[C:3](=[O:23])[C:4]1[C:9]([Cl:10])=[CH:8][C:7]([Cl:11])=[CH:6][C:5]=1[NH:12][C:13](=[O:22])[CH:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:15].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C[Si](C)(C)[N-][Si](C)(C)C.[Li]CCCC>C1COCC1>[Cl:10][C:9]1[CH:8]=[C:7]([Cl:11])[CH:6]=[C:5]2[C:4]=1[C:3](=[O:23])[C:14]([CH3:15])([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[C:13](=[O:22])[NH:12]2

Participants

6

Reactant 4

HCID 2733832Lithium HexamethyldisilazideHCID 3280088Npc316347HCID 68817719HCID 68817719, compoundHCID 178418339Butyllithium

Product 1

HCID 11638332HCID 11638332, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a pre-cooled (−78° C.) solution of 4,6-dichloro-2-(2-phenyl-propionyl amino)-benzoic acid methyl ester (0.82 g, 2.30 mmol) in dry THF (70 mL) was added dropwise LiHMDS [prepared by treatment of a hexamethyldisilazide (1.47 mL, 6.90 mmol) in dry THF (25 mL) with n-BuLi (3.70 mmol, 2.5M hexane solution) for 1 hour at −78° C.]. The reaction mixture was stirred for 1 hour and then refluxed overnight under a nitrogen atmosphere. After cooling to room temperature, the reaction was quenched by the addition of 1N HCl aqueous solution. Subsequently, the resultant was extracted with ethyl acetate (150 mL×3), and organic phase was washed with brine (150 mL×2) and water (150 mL×2) dried with magnesium sulfate. After evaporation the solvent, an objective compound (0.57 g, 78%) was obtained as yellow solid by a flash column chromatography (Hexane:EtOAc=4:1): 1H NMR (200 MHz, CD3OD+DMSO-d6) δ 1.61 (s, 3H, CH3), 6.96 (m, 1H, ArH), 7.08-7.34 (m, 6H, ArH); m.p. 222-225° C.; MS(EI) m/e 319 [M+], 285, 132, 104.

Workup

  1. temperaturerefluxed overnight under a nitrogen atmosphere
  2. customthe reaction was quenched by the addition of 1N HCl aqueous solution
  3. extractionSubsequently, the resultant was extracted with ethyl acetate (150 mL×3), and organic phase
  4. washwas washed with brine (150 mL×2) and water (150 mL×2)
  5. dry with materialdried with magnesium sulfate
  6. customAfter evaporation the solvent

Sources & evidence

ORD record
ord-9ce4d64b242648ae91d899b3181ba4b6
Source dataset
uspto-grants-2009_09
Patent number
US07592457B2

Reaction notes

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