Cyclopropylboronic acid → 8-Benzyl-3-cyclopropyl-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine

HRID 518037Notes

Reaction equation

[CH2:1]([N:8]1[CH2:14][C:13]2[N:15]=[CH:16][C:17](Cl)=[N:18][C:12]=2[O:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:20]1(B(O)O)[CH2:22][CH2:21]1.C1(P(C2CC2)C2CC2)CC1.CC(C)([O-])C.[K+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH2:1]([N:8]1[CH2:14][C:13]2[N:15]=[CH:16][C:17]([CH:20]3[CH2:22][CH2:21]3)=[N:18][C:12]=2[O:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A suspension of 8-benzyl-3-chloro-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine (493 mg), cyclopropylboronic acid (280 mg), palladium acetate (20 mg), tricyclopropylphosphine (51 mg) and potassium tert-butoxide (663 mg) in toluene (8 mL) was stirred under an argon atmosphere with heating at 100° C. for 2 hr. Water was added to the reaction mixture, the aqueous layer was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient: 5→25% ethyl acetate/hexane) to give the title compound (79.9 mg, 16%) as a colorless oil.

Workup

extractionthe aqueous layer was extracted with ethyl acetate
washthe organic layer was washed with saturated brine
dry with materialdried over anhydrous magnesium sulfate
concentrationconcentrated under reduced pressure
customThe obtained residue was purified by silica gel column chromatography (solvent gradient: 5→25% ethyl acetate/hexane)

Sources & evidence

ORD record: ord-c533418b47af4ab6856aa35ae89dd03a
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115139B2

Reaction notes

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