1,2-Dimethoxyethane → (S)-2'-bromo-7'-(pyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthen]-2-amine

HRID 1970386Notes

Reaction equation

[Br:1][C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8](I)=[CH:9][CH:10]=3)[C@@:5]3([CH2:20][O:19][C:18]([NH2:21])=[N:17]3)[C:4]=2[CH:3]=1.[N:22]1[CH:27]=[CH:26][CH:25]=[C:24](B(O)O)[CH:23]=1.COCCOC.C(=O)([O-])[O-].[Na+].[Na+]>O.C(OCC)(=O)C.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>[Br:1][C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([C:24]4[CH:23]=[N:22][CH:27]=[CH:26][CH:25]=4)=[CH:9][CH:10]=3)[C@@:5]3([CH2:20][O:19][C:18]([NH2:21])=[N:17]3)[C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 70 °C

Procedure

A 100 ml RB flask was charged with (R)-2′-bromo-7′-iodo-5H-spiro[oxazole-4,9′-xanthen]-2-amine (3.3 g, 7.22 mmol), pyridin-3-ylboronic acid (1.163 g, 9.39 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.834 g, 0.722 mmol). To this were added DME (51.6 mL) followed by sodium carbonate (10.83 mL, 21.66 mmol) (2M solution) and the mixture was heated at 70° C. for 24 hrs. The mixture was diluted with water and ethyl acetate, filtered and organic layer was separated and concentrated. The crude material was purified by FC on 80 g RediSep column using 5-70% gradient of DCM/MeOH/NH4OH in DCM to give (S)-2′-bromo-7′-(pyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine (1.82 g, 4.45 mmol, 61.6% yield).

Workup

filtrationfiltered
customorganic layer was separated
concentrationconcentrated
customThe crude material was purified by FC on 80 g RediSep column

Sources & evidence

ORD record: ord-733b9719ec794ec091b396465a76bf01
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08426447B2

Reaction notes

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