Dimedone → HCID 90014535, compound

HRID 626435Notes

Reaction equation

HRID 626435 reaction equation
C(OC([NH:7][C@H:8]([C:15]([NH:17][C:18]1[CH:19]=[C:20]([CH2:25][C@@H:26]([CH3:32])[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:21]=[CH:22][C:23]=1[Cl:24])=[O:16])[CH:9]([C:11]([F:14])([F:13])[F:12])[CH3:10])=O)C=C.CC1(C)CC(=O)CC(=O)C1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1COCC1>[Cl:24][C:23]1[CH:22]=[CH:21][C:20]([CH2:25][C@@H:26]([CH3:32])[C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:19][C:18]=1[NH:17][C:15](=[O:16])[C@H:8]([CH:9]([C:11]([F:14])([F:13])[F:12])[CH3:10])[NH2:7]

Participants

5

Reactant 2

HCID 31358DimedoneHCID 126504139HCID 126504139, compound

Product 1

HCID 90014535HCID 90014535, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

1.40 g (2.92 mmol) of ethyl (2R)-3-[3-({N-[(allyloxy)carbonyl]-4,4,4-trifluorovalyl}amino)-4-chlorophenyl]-2-methylpropanoate (Example 38A, mixture of 4 isomers) and 3.28 g (23.4 mmol) of dimedone were initially charged in 10 ml of abs. THF. At RT, the solution was deoxygenated by passing through argon for 30 min. Subsequently 67.6 mg (0.058 mmol) of tetrakis(triphenylphosphine)palladium(0) were added and the mixture was stirred at RT overnight. After dilution with ethyl acetate, the mixture was washed twice with sat. sodium bicarbonate solution and once with sat. sodium chloride solution. The organic phase was dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 40:1→20:1) and separated. This gave 844 mg of the target compound as diastereomer mixture 1 (73.1% of theory).

Workup

  1. customAt RT, the solution was deoxygenated
  2. washAfter dilution with ethyl acetate, the mixture was washed twice with sat. sodium bicarbonate solution and once with sat. sodium chloride solution
  3. dry with materialThe organic phase was dried over magnesium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 40:1→20:1)
  6. customseparated

Sources & evidence

ORD record
ord-de20153cef634328acf4ef8d06ca6405
Source dataset
uspto-grants-2016_04
Patent number
US09309198B2

Reaction notes

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