Tricyclohexylphosphine → HCID 117843984, compound

HRID 2209309Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[N:9]([CH3:23])[C:10]([CH:12]1[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]1)=[O:11].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.CC(C)([O-])C.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:8][C:5]1[CH:4]=[C:3]2[C:2]([C:12]3([CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]3)[C:10](=[O:11])[N:9]2[CH3:23])=[CH:7][CH:6]=1

Participants

Conditions

Temperature: 80 °C

Procedure

tert-butyl 3-((2-bromo-5-chlorophenyl)(methyl)carbamoyl)azetidine-1-carboxylate 7.57 (112 mg, 0.28 mmol), palladium acetate (6.6 mg, 0.03 mmol), tricyclohexylphosphine (8.4 mg, 0.03 mmol), and sodium t-butoxide (42 mg, 0.44 mmol) were added to a flask and system was evacuated and placed under argon. Dioxane (2 mL) was added and mixture was heated at 80° C. for 20 hours. After cooling to rt, mixture was poured into 50% saturated NH4Cl(aq) and extracted with ethyl acetate. Layers were separated and organics were dried (Na2SO4), filtered, and concentrated under reduced pressure. The resulting residue was purified via silica gel column chromatography (0-30% ethyl acetate/hexanes) to yield tert-butyl 6′-chloro-1′-methyl-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate 7.58 (63 mg).

Workup

customsystem was evacuated
additionDioxane (2 mL) was added
temperatureAfter cooling to rt
additionmixture was poured into 50% saturated NH4Cl(aq)
extractionextracted with ethyl acetate
customLayers were separated
dry with materialorganics were dried (Na2SO4)
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe resulting residue was purified via silica gel column chromatography (0-30% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-8ea5dba376db4af59310ec92bb4040d6
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09376441B2

Reaction notes

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