Ethyl 3,3-diethoxypropionate → HCID 67772187, compound

HRID 1963079Notes

Reaction equation

HRID 1963079 reaction equation
C(O[C:4]([C:6]1[N:7]([NH2:26])[CH:8]=[C:9]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:19]=2[CH3:25])[C:10]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:5])C.[CH2:27]([O:29][CH:30]([O:37]CC)[CH2:31][C:32](OCC)=O)[CH3:28].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1CCN2C(=NCCC2)CC1>CN(C=O)C.O>[CH2:27]([O:29][C:30]([C:31]1[C:4](=[O:5])[C:6]2[N:7]([CH:8]=[C:9]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:19]=3[CH3:25])[C:10]=2[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[NH:26][CH:32]=1)=[O:37])[CH3:28]

Participants

7

Reactant 4

HCID 66389Ethyl 3,3-diethoxypropionateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 521998p-Toluenesulfonic acid monohydrateHCID 67773630HCID 67773630, compound

Product 1

HCID 67772187HCID 67772187, compoundYield 75.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of the compound of step 5 (6.290 g, 17.85 mmol) in 180 ml of anhydrous DMF under nitrogen were added ethyl 3,3-diethoxy-propanoate (10.42 ml, 53.55 mmol) and p-toluenesulfonic acid hydrate (0.509 g, 2.68 mmol), and the solution was heated at 90° C. for 1.5 h. After cooling to 60° C., DBU (13.32 ml, 89.24 mmol) was added dropwise and the mixture was stirred for 45 min at 60° C. The solution was then cooled to room temperature, water (600 ml) was added and the solution was extracted four times with EA (200 ml). The combined organic phases were washed with 0.5 N hydrochloric acid (300 ml) and brine (300 ml), dried over magnesium sulfate, filtered and evaporated to dryness under reduced pressure. The residue was triturated several times with cyclohexane and dried in vacuo at 50° C. 5.43 g of the title compound were obtained as a brown solid melting at 176-177° C.

Workup

  1. temperatureAfter cooling to 60° C.
  2. temperatureThe solution was then cooled to room temperature
  3. extractionthe solution was extracted four times with EA (200 ml)
  4. washThe combined organic phases were washed with 0.5 N hydrochloric acid (300 ml) and brine (300 ml)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness under reduced pressure
  8. customThe residue was triturated several times with cyclohexane
  9. customdried in vacuo at 50° C

Sources & evidence

ORD record
ord-cc5e91ce15904f50b6861caa5d33f6bf
Source dataset
uspto-grants-2013_04
Patent number
US08415336B2

Reaction notes

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