Benzaldehyde → HCID 22612040, compound

HRID 844072Notes

Reaction equation

HRID 844072 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:29]=[CH:28][C:17]([O:18][C:19]2[C:24]([C:25](=[O:27])[CH3:26])=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:16][CH:15]=1.[CH:30](=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>O1CCCC1.CCCCCC>[F:13][C:14]1[CH:15]=[CH:16][C:17]([O:18][C:19]2[C:24]([C:25](=[O:27])[CH2:26][CH:30]([OH:37])[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:28][CH:29]=1

Participants

7

Reactant 4

HCID 240BenzaldehydeHCID 7912DiisopropylamineHCID 22612228HCID 22612228, compoundHCID 178418339Butyllithium

Product 1

HCID 22612040HCID 22612040, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

A solution of 0.114 mL (111 mg, 1.10 mmol) of diisopropylamine in 8 mL of tetrahydrofuran was cooled to −78° C. and treated dropwise with 0.440 mL (1.10 mmol) of a solution of 2.5 M n-butyllithium in hexane. After stirring for 30 min, a solution of 231 mg (1.00 mmol) 1-[2-(4-Fluorophenoxy)-3-pyridinyl]-ethanone in 2 mL of tetrahydrofuran was added dropwise. After stirring for 30 min, 0.112 mL (1.07 mmol) of benzaldehyde was added dropwise, and stirring was continued for 1 h. The mixture was quenched by the addition of 2 mL of saturated aqueous NH4Cl solution and was allowed to warm to rt. The mixture was partitioned between 50 mL of saturated aqueous NH4Cl solution and 300 mL of EtOAc. The separated organic layer was washed with 50 mL of saturated aqueous sodium hydrogencarbonate solution, 50 mL of brine, dried (Na2SO4), and evaporated to 259 mg of an oil. Purification by flash chromatography using a 40% EtOAc-hexane eluant afforded 211 mg (63% yield) of the title compound as an oil; 1H NMR (CDCl3) d 3.23 (1H, br s), 3.54-3.56 (2H, m), 5.34-5.37 (1H, m), 7.07-7.41 (10H, m), 8.21-8.26 (2H, m); APCI MS (m/e) 338 (M++1).

Workup

  1. stirringAfter stirring for 30 min
  2. stirringstirring
  3. waitwas continued for 1 h
  4. customThe mixture was quenched by the addition of 2 mL of saturated aqueous NH4Cl solution
  5. customThe mixture was partitioned between 50 mL of saturated aqueous NH4Cl solution and 300 mL of EtOAc
  6. washThe separated organic layer was washed with 50 mL of saturated aqueous sodium hydrogencarbonate solution, 50 mL of brine
  7. dry with materialdried (Na2SO4)
  8. customevaporated to 259 mg of an oil
  9. customPurification by flash chromatography

Sources & evidence

ORD record
ord-9b04f61e563d47a3b06d8874dfffdf7f
Source dataset
uspto-grants-2002_04
Patent number
US06380218B1

Reaction notes

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