Hydrochloric Acid → HCID 14770849, compound

HRID 1090387Notes

Reaction equation

HRID 1090387 reaction equation
[C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([O-:5])=O.C([Li])CCC.[C:15]([NH:18][CH:19]1[CH2:23][CH2:22][CH:21]([C:24]2[C:32]([F:33])=[CH:31][C:27](C(Cl)=O)=[C:26]([F:34])[CH:25]=2)[CH2:20]1)(=[O:17])[CH3:16].Cl>CCCCCC.O1CCCC1.N1C=CC=CC=1C1C=CC=CN=1.O>[C:15]([NH:18][CH:19]1[CH2:23][CH2:22][CH:21]([C:24]2[C:32]([F:33])=[CH:31][C:27]([C:3](=[O:5])[CH2:2][C:1]([O:7][CH2:8][CH3:9])=[O:6])=[C:26]([F:34])[CH:25]=2)[CH2:20]1)(=[O:17])[CH3:16]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 3595298Propanedioic acid, monoethyl esterHCID 14770848HCID 14770848, compoundHCID 178418339Butyllithium2×

Product 1

HCID 14770849HCID 14770849, compoundYield 90%

Reagents, catalysts & solvents 4

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

Procedure

A solution of 26.4 g (0.2 mol) of monoethyl malonate, 0.1 g of 2,2'-bipyridyl and 350 ml of dry tetrahydrofuran was cooled to -35° under a 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 30.2 g (0.1 mol) of 4-[3-(acetylamino) cyclopentyl]-2,5 difluorobenzoyl chloride in 150 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 ml-0.20 mol). The organic phase 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 31.8 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 phase 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-363a04fab637430f8f3d958bcd0b00c1
Source dataset
uspto-grants-1992_01
Patent number
US05081254

Reaction notes

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