Ethyl 3-bromopropionate → 4-Cyano-4-(3,4-dichlorophenyl)-7-(tetrahydropyran-4-yloxy)-heptanoic Acid Ethyl Ester

HRID 394542Notes

Reaction equation

HRID 394542 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[K+].[Cl:11][C:12]1[CH:13]=[C:14]([CH:19]([CH2:22][CH2:23][CH2:24][O:25][CH:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[C:20]#[N:21])[CH:15]=[CH:16][C:17]=1[Cl:18].Br[CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36]>C1COCC1>[CH2:38]([O:37][C:35](=[O:36])[CH2:34][CH2:33][C:19]([C:20]#[N:21])([C:14]1[CH:15]=[CH:16][C:17]([Cl:18])=[C:12]([Cl:11])[CH:13]=1)[CH2:22][CH2:23][CH2:24][O:25][CH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1)[CH3:39]

Participants

5

Reactant 3

HCID 68320Ethyl 3-bromopropionateHCID 3251421Potassium bis(trimethylsilyl)amideHCID 158876512-(3,4-Dichloro-phenyl)-5-(tetrahydro-pyran-4-yloxy)-pentanenitrile

Product 1

HCID 158876524-Cyano-4-(3,4-dichlorophenyl)-7-(tetrahydropyran-4-yloxy)-heptanoic Acid Ethyl EsterYield 94.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Potassium hexamethyldisilazide (0.5 M in toluene, 285 mL, 0.143 mol) was added dropwise to a solution of (4) (39 g, 0.119 mol) in THF (240 mL) under nitrogen and stirred at room temperature for 1 hour. A solution of ethyl 3-bromopropionate (22.8 mL, 0.178 mol, 1.5 eq) in THF (45 mL) was added to the reaction mixture all at once. After stirring at room temperature for 4 hours, the reaction was quenched with saturated NH4Cl solution (20 mL). The organic solution was dried over MgSO4, and solvent is evaporated. The crude oil was purified by flashed chromatography (hexane-AcOEt/8:1) to give light yellow oil (48.03 g, 94.4% yield).

Workup

  1. stirringAfter stirring at room temperature for 4 hours
  2. customthe reaction was quenched with saturated NH4Cl solution (20 mL)
  3. dry with materialThe organic solution was dried over MgSO4, and solvent
  4. customis evaporated
  5. customThe crude oil was purified

Sources & evidence

ORD record
ord-b5876a007b914612bf408d14abdbe7ad
Source dataset
uspto-grants-2003_08
Patent number
US06602886B2

Reaction notes

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