Diisopropylamine → HCID 58566374, compound

HRID 2069628Notes

Reaction equation

HRID 2069628 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([F:23])[CH:16]=1)#[CH:14].Cl[C:25]([O:27][CH2:28][CH3:29])=[O:26]>O1CCCC1>[F:23][C:17]1[CH:16]=[C:15]([C:13]#[C:14][C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH:20]=[CH:19][C:18]=1[O:21][CH3:22]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 10928Ethyl chloroformateHCID 64319824-ethynyl-2-fluoro-1-methoxybenzeneHCID 178418339Butyllithium

Product 1

HCID 58566374HCID 58566374, compoundYield 33.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To the mixture of diisopropylamine (0.262 mL, 1.87 mmol) in tetrahydrofuran (5 mL) at −78° C. under nitrogen was added slowly the solution of n-butyllithium (1.17 mL, 1.87 mmol, 1.6M in hexanes). After stifling for 30 minutes, the solution of 4-ethynyl-2-fluoro-1-methoxybenzene (622) (0.180 g, 0.94 mmol) in tetrahydrofuran (1 mL) was added slowly into the reaction mixture. The mixture was allowed to reach 0° C. over 1 hour and ethyl chloroformate (0.134 mL, 1.4 mmol) was added. The resulting mixture was stirred to room temperature for 12 hours, quenched with saturated ammonium chloride and extracted with ethyl ether. The organic phase was washed with water, brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (5-10% EtOAc in hexanes) to provide ethyl 3-(3-fluoro-4-methoxyphenyl)propiolate (623) (0.070 g, 6.3%) as a colorless oil.

Workup

  1. waitto reach 0° C. over 1 hour
  2. customquenched with saturated ammonium chloride
  3. extractionextracted with ethyl ether
  4. washThe organic phase was washed with water, brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography on silica gel (5-10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-066935c1df944a09854cf2ef6998e382
Source dataset
uspto-grants-2012_10
Patent number
US08299117B2

Reaction notes

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