Diazomethane → rel-(3S,5S)-7-Chloro-5-(2-cyclopropylethynyl)-1,5-dihydro-3-cyclopropyl-5-(trifluoromethyl)-4,1-benzoxazepin-2(3H)-one

HRID 369751Notes

Reaction equation

HRID 369751 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10](=[O:12])[C@H:9]([CH:13]=[CH2:14])[O:8][C@:7]([C:19]#[C:20][CH:21]3[CH2:23][CH2:22]3)([C:15]([F:18])([F:17])[F:16])[C:6]=2[CH:24]=1.[N+](=[CH2:27])=[N-]>CCOCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10](=[O:12])[C@H:9]([CH:13]3[CH2:27][CH2:14]3)[O:8][C@:7]([C:19]#[C:20][CH:21]3[CH2:23][CH2:22]3)([C:15]([F:16])([F:17])[F:18])[C:6]=2[CH:24]=1

Participants

5

Reactant 2

HCID 9550DiazomethaneHCID 56994752rel-(3S,5S)-7-Chloro-5-(2-cyclopropylethynyl)-1,5-dihydro-3-ethen yl-5-(trifluoromethyl)-4,1-benzoxazepin-2(3H)-one

Product 1

HCID 57119190rel-(3S,5S)-7-Chloro-5-(2-cyclopropylethynyl)-1,5-dihydro-3-cyclopropyl-5-(trifluoromethyl)-4,1-benzoxazepin-2(3H)-oneYield 88.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 3283Diethyl EtherSolvent2×

Procedure

To a solution of 71 mg of rel-(3S,5S)-7-chloro-5-(2-cyclopropylethynyl)-1,5-dihydro-3-ethenyl-5-(trifluoromethyl)-4,1-benzoxazepin-2(3H)-one (from Example 41) in 7.5 mL of anhydrous ether was added first 4 mg of palladium (II) acetate and then a solution of approximately 1.23 mmol of diazomethane in 3.5 mL of ether. After stirring 30 min at room temperature, the reaction mixture was filtered through a pad of filter-aid and the filtrate was evaporated to dryness. The crude product was purified by column chromatography over silica gel (elution with methylene chloride) to give 65 mg of the title compound as a pure solid was recrystallized from ether-hexanes to afford 36 mg: mp 192-192.50; HRMS: Calcd. for C18H14NO2F3Cl (M-H)- : 368.0665. Found: 368.0657.

Workup

  1. filtrationthe reaction mixture was filtered through a pad
  2. filtrationof filter-aid
  3. customthe filtrate was evaporated to dryness
  4. customThe crude product was purified by column chromatography over silica gel (elution with methylene chloride)

Sources & evidence

ORD record
ord-0204117eb312494190b0581af5f30044
Source dataset
uspto-grants-2000_10
Patent number
US06140320

Reaction notes

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