Hydrochloric Acid → HCID 14770855, compound

HRID 1090391Notes

Reaction equation

HRID 1090391 reaction equation
[C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([O-:5])=O.C([Li])CCC.[O:15]1[C:19]2([CH2:23][CH2:22][CH:21]([C:24]3[C:29]([F:30])=[CH:28][C:27](C(N4C=CN=C4)=O)=[C:26]([F:38])[CH:25]=3)[CH2:20]2)[O:18][CH2:17][CH2:16]1.Cl>CCCCCC.O1CCCC1.N1C=CC=CC=1C1C=CC=CN=1.O>[F:38][C:26]1[CH:25]=[C:24]([CH:21]2[CH2:22][CH2:23][C:19]3([O:15][CH2:16][CH2:17][O:18]3)[CH2:20]2)[C:29]([F:30])=[CH:28][C:27]=1[C:3](=[O:5])[CH2:2][C:1]([O:7][CH2:8][CH3:9])=[O:6]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 3595298Propanedioic acid, monoethyl esterHCID 14770854HCID 14770854, compoundHCID 178418339Butyllithium2×

Product 1

HCID 14770855HCID 14770855, compoundYield 77.9%

Reagents, catalysts & solvents 4

HCID 14742,2'-BipyridineCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent2×

Procedure

A solution of 16.4 g (0.2 mol) of monoethyl malonate, 0.1 g of 2,2'-bipyridyl and 175 ml of dry tetrahydrofuran was cooled to -35° under a dry nitrogen atmosphere and treated dropwise with 80 ml (0.2 mol) of a 2.5 M solution of n-butyl lithium in hexane. After the addition was complete, the reaction mixture was allowed to warm to -5° where it was treated dropwise with 80 ml (0.2 mol) of 2.5 M n-butyl lithium in hexane, titrating the final addition to a pale pink color which persisted for 5 minutes. The mixture was cooled to -78° and treated with a solution of 16.7 g (50 mmol) of 1-[[4-(1,4-dioxaspiro[4.4]non-7-yl)-2,5 difluorophenyl]carbonyl]-1H-imidazole in 100 ml of dry tetrahydrofuran. The suspension was stirred at -78° for 45 minutes, then allowed to warm to -35° and poured into a mixture of ice, water, and concentrated hydrochloric acid (17.0 ml-0.2 mole). The organic layer was separated, washed with water, 5% sodium bicarbonate, dilute hydrochloric acid, and water. After drying over magnesium sulfate, the solvent was removed in vacuo to give 13.8 g of the title compound.

Workup

  1. additionAfter the addition
  2. temperatureto warm to -5° where it
  3. additionaddition to a pale pink color which
  4. temperatureThe mixture was cooled to -78°
  5. temperatureto warm to -35°
  6. customThe organic layer was separated
  7. washwashed with water, 5% sodium bicarbonate, dilute hydrochloric acid, and water
  8. dry with materialAfter drying over magnesium sulfate
  9. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-2336667f2ec74c84b1eec5a2d7c063ca
Source dataset
uspto-grants-1992_01
Patent number
US05081254

Reaction notes

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